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Ayoub Ali Alshaikh,1,* Syed Esam Mahmood,1,* Fatima Riaz,1,* Ahmed Shubayli Assiri,2,* Majdoleen A Abdulrahman,3,* Mohammed Yahya Althwabi Asiri,3,* Ghadeer Redha Abdullah Alnakhli,4,* Mohanad Qasem A Alshabab,3,* Saud Saeed Abdullah Alsaleh,5,* Majed Yahya Alshahrani,6,* Amnah Saad H Alharthi,7,* Amar Abdullah Al Qahtani7,* 1Department of Family & Community Medicine, College of Medicine, King Khalid University, Abha, 62529, Saudia Arabia; 2Consultant Family Medicine, Ministry of Health, Aseer Region, Abha, Saudia Arabia; 3Saudi Board of Family Medicine, Abha, Saudi Arabia; 4Saudi Board of Pediatric Neurology, Abha, Saudi Arabia; 5Saudi Board of Internal Medicine, Abha, Saudi Arabia; 6Saudi Board of General Medicine, Abha, Saudi Arabia; 7College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia*These authors contributed equally to this workCorrespondence: Syed Esam Mahmood, Department of Family and Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia, Email smahmood@kku.edu.saIntroduction: Many studies report a lack of public awareness of the risk factors and complications of Diabetes Mellitus. Adequate glycemic control is crucial in preventing or delaying the onset of type 2 diabetes complications, and medication adherence is one of the key factors in achieving this goal. This study aimed to measure the knowledge about diabetes mellitus and practices regarding lifestyle factors and diabetes management in the study population in the Aseer region, of Saudi Arabia.Material and Methods: A descriptive cross-sectional survey was conducted in Abha, a city in the Aseer region of Saudi Arabia. The general population of 18 years of age and above, who were residing in the study area during the period of study, ie, January 2023 to June 2023, were included. The questionnaire was distributed through social media and e-mail for data collection. The descriptive variables were presented using frequency, percentage, and graphs. Pearson’s chi-square test was used at a 5% level of significance. Multivariate tests were applied to further explore the findings of univariate analysis. The data were analyzed using SPSS version 20.0.Results: Out of the total 348 participants, a higher proportion was males (56.3%). About 78.7% of the participants were ever diagnosed with diabetes mellitus and 21.3% were never diagnosed with diabetes mellitus. Nearly 31.6% knew that the major cause of diabetes mellitus was obesity and 31.3% knew that it was a hereditary disease. About 42.2% of respondents exercised regularly and 27.6% were smokers. Adherence to prescribed anti-diabetic medications was seen in 63.2% of the respondents. Self-alterations in the timing and dose of prescribed anti-diabetic drugs were seen in 36.5% and 34.8%, respectively. About 60.1% had a moderate level of self-rated knowledge about Diabetes Mellitus, and 27.6% and 12.4% had good and poor self-rated knowledge levels of Diabetes mellitus, respectively. On multivariate analysis, the age group 60– 69 years had significant variations as compared to the other age groups on DM, bachelor’s degree holders had significant variations as compared to other education variables, being married had significant differences as compared to those unmarried, those employed had significant variations as compared to the other occupation categories, and smokers had a significant impact on DM as compared to non-smokers.Conclusion: Findings indicated less number of respondents exercised regularly, low adherence to prescribed anti-diabetic medications and low levels of self-rated knowledge of diabetes mellitus. Enhancing the patients’ knowledge of diabetes mellitus and improving their self-management and adherence to its medications is necessary through public health education.Keywords: adherence, diabetes mellitus, management, aseer region

Noha A Kamel,1 Mahmoud S Abdalla,2 Amer Al Ali,3 Mohammad Y Alshahrani,4 Khaled M Aboshanab,5,6 Mervat I El Borhamy1,7 1Department of Microbiology, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt; 2Hematology and Bone Marrow Transportation (BMT) Unit, International Medical Center (IMC), Cairo, Egypt; 3Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, University of Bisha, Bisha, 67714, Saudi Arabia; 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, 9088, Saudi Arabia; 5Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; 6Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University Technology MARA (Uitm), Campus Puncak Alam, Bandar Puncak Alam, Selangor, 42300, Malaysia; 7International Medical Center, Clinical Microbiology Laboratory, Cairo, EgyptCorrespondence: Khaled M Aboshanab, Tel +20-01007582620, Fax +20-(202)24051107, Email aboshanab2012@pharma.asu.edu.eg; khaledaboshanab@uitm.edu.egObjective: Owing to the rising incidence of multidrug-resistant organisms (MDRO) and the high mortality rates associated with such bacterial infections post-hematopoietic stem cell transplantation (HSCT), we investigated the MDRO colonization rate prior to transplantation using an active surveillance approach and determined its impact on subsequent infection during the pre-engraftment period.Methods: A single-center observational study was conducted, and surveillance cultures from multiple body sites, including the rectum, nasal cavity, and groin, were performed at admission to determine MDRO colonization. Serological tests were used to detect certain viruses and toxoplasmosis before HSCT.Results: In the pre-transplant setting, 59 MDRO were recovered from the 40 HSCT recipients. Of the 59 isolates recovered from one or more body sites, 29 were positive for methicillin-resistant Staphylococcus aureus (MRSA), 7 for carbapenem-resistant Enterobacterales (CRE), and 23 were positive for extended-spectrum β-lactamase (ESBLs). Serological assessment before HSCT revealed active or reactivation of latent infection with cytomegalovirus (7.5%), Epstein–Barr virus (EBV; 5%), and Toxoplasma gondii (2.5%) among HSCT patients. In terms of factors associated with pre-engraftment infections, the type of transplant (p=0.04) was statistically significant, whereas other factors, such as age, sex, and underlying conditions, were not. In post-transplant settings, bloodstream infections (BSIs) were documented in 2 allogeneic HSCT patients (5%), and the isolated microorganisms were ESBL-producing E. coli and non-MDR Acinetobacter baumannii.Conclusion: Active screening cultures are a helpful tool for identifying patients colonized by MDRO or relevant viruses before HSCT, and for predicting those at risk of developing subsequent pre-engraftment infections. Additionally, active screening may aid in predicting those who are likely to develop subsequent pre-engraftment infections Our findings highlight the importance of pre-transplant screening for high-priority multidrug-resistant pathogens and the application of infection control interventions after HSCT.Keywords: pre-transplant screening, MRSA, ESBLs, CRE, pre-engraftment infections

Alanoud Aladel,1,&ast; Amit K Verma,2,&ast; Sadaf Dabeer,3 Irfan Ahmad,4 Mohammad Y Alshahrani,4 Mohammad S AboHassan,4 Mohammad Idreesh Khan,5,&ast; Malak Ghazi Almutairi,6 Mirza Masroor Ali Beg7,8 1Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 2Department of Biotechnology, Jamia Millia Islamia, New Delhi, India; 3Division of Endocrinology Metabolism, and Lipids, School of Medicine, Emory University, Atlanta, GA, USA; 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; 5Department of Clinical Nutrition, College of Applied Health Sciences in Arras, Qassim University, Buraidah, Saudi Arabia; 6Department of Nutrition, Almethnab General Hospital, Qassim Health Cluster, Ministry of Health, Al Mithnab, Saudi Arabia; 7Faculty of Medicine, Alatoo International University, Bishkek, Kyrgyzstan; 8Centre for Promotion of Medical Research, Bishkek, Kyrgyzstan&ast;These authors contributed equally to this workCorrespondence: Mirza Masroor Ali Beg, Email mirzamasroor1986@gmail.comBackground: Type 2 diabetes mellitus (T2DM) has risen to become the world’s most serious public health problem in recent years, and the role of long noncoding RNAs (lncRNAs) in the onset and progression of T2DM, as well as special attention to vitamins, has gotten a lot of attention recently.Methods: The aim of the study was to analyze lncRNA LINC01173 expression along with assessment of vitamin-D and B12 among the T2DM cases. Quantitative RT-PCR was used to analyze the expression of lncRNA LINC01173. Vitamin-D and B12 were analyzed by chemiluminescence-based assay.Results: The present study observed that the T2DM cases had 6.67-fold increased lncRNA LINC01173 expression compared to healthy controls. Expression of lncRNA LINC01173 was found to be associated with hypertension (p=0.03), wound healing (p=0.04), and blurred vision (p< 0.0001). It was observed that the T2DM cases with vitamin-D deficiency had a significant association with fasting glucose level (p=0.01) and HbA1C level (p=0.01) among the T2DM cases. The association of lncRNA LINC01173 with vitamin-D was analyzed and it was observed that the vitamin-D deficient cases had higher lncRNA LINC01173 expression compared to insufficient T2DM cases (p=0.01) and sufficient T2DM cases (p=0.0006). It was also observed that the T2DM cases with smoking had a 8.33-fold lncRNA LINC01173 expression while non-smokers had a 5.43-fold lncRNA LINC01173 expression (p< 0.0001).Conclusion: The study concluded that the increased lncRNA LINC01173 expression was observed to be linked with alteration in vitamin-D level and smoking habit. Altered expression of lncRNA LINC01173 expression was linked with fasting glucose and HbA1C alteration. Collectively, lncRNA LINC01173 expression, vitamin-D alteration, as well as smoking habit may cause the disease severity and increase the pathogenesis of disease.Keywords: long noncoding RNA, vitamin-D, vitamin-B12, diabetes

Bayapa Reddy Narapureddy,1 Khursheed Muzammil,1 Mohammad Yahya Alshahrani,2 Ali G Alkhathami,2 Abdullah Alsabaani,3 Abdullah M AlShahrani,4 Adam Dawria,1 Nazim Nasir,4 Lingala Kalyan Viswanath Reddy,5 Mohammad Mahtab Alam6 1Department of Public Health, College of Applied Medical Sciences, Khamis Mushayt, King Khalid University, Abha, 62561, Kingdom of Saudi Arabia; 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Abha, King Khalid University, Abha, 9088, Kingdom of Saudi Arabia; 3Department of Family and Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia; 4Department of Basic Medical Sciences, College of Applied Medical Sciences, Khamis Mushayt, King Khalid University, Abha, 62561, Kingdom of Saudi Arabia; 5Department of Public Health, College of Health Sciences, Saudi Electronic University, Abha, 62561, Kingdom of Saudi Arabia; 6Department of Basic Medical Sciences, College of Applied Medical Science, Abha, King Khalid University, Abha, 62561, Kingdom of Saudi ArabiaCorrespondence: Bayapa Reddy NarapureddyDepartment of Public Health, College of Applied Medical Sciences, Khamis Mushayt, King Khalid University, Abha, 62561, Kingdom of Saudi ArabiaTel +966-55714527Email bapureddy@kku.edu.saIntroduction: COVID-19 was declared a pandemic in March 2020 by the World Health Organization. Control of COVID-19 depends on the potential vaccine and its successful delivery to a large portion of the population to develop herd immunity. All the governments have made a robust plan to distribute the vaccine to their people, but many countries could not achieve adequate vaccination coverage. Hence, this study explores people’s beliefs and barriers to vaccination and provides valuable inputs to the government to attain adequate vaccination.Objective: To know the knowledge level about the COVID-19 vaccine among the residents of KSA. To find out the various concerns (beliefs) about COVID-19 and its vaccine among the residents of KSA. To estimate the vaccine acceptance and understand the barriers to accepting the COVID-19 vaccine among residents of KSA.Materials and Methods: A web-based, cross-sectional study was conducted from April to June 2021 in a restricted environment on the adult (> 18 years) residents of Saudi Arabia. The minimum calculated sample was 685; 796 study samples were finally studied to minimize the sampling error. Snowball sampling was used to select the study samples, after meeting the inclusion criteria.Results: A total of 796 people responded. Only 782 (98.2%) were finally considered after excluding the incomplete information forms. The selected participant’s age ranges from 18 years to 80 years. Almost 723 (92%) of the study group knew COVID vaccines. Most of the participants, 370 (47%), preferred USA-manufactured vaccine followed by Saudi Arabia 217 (28%). A total of 259 (33.1%) participants were hesitant to receive the vaccine. Out of 782, half of the participants, 386 (50%), believed the COVID vaccine will prevent the infection.Conclusion: The government must implement appropriate culturally accepted interventional vaccination educational campaigns to remove the beliefs, worries regarding the safety and efficacy of COVID-19 vaccines, to increase vaccine acceptance rates.Keywords: COVID-19, public willingness, vaccine, vaccine hesitancy, vaccine acceptance, Saudi Arabia

Mohamed Adam,1 Moawia Gameraddin,2 Magbool Alelyani,1 Mohammad Y Alshahrani,3 Awadia Gareeballah,2 Irshad Ahmad,4 Abdulrahman Azzawi,5 Basem Komit,6 Alamin Musa1 1Department of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; 2Department of Diagnostic Radiologic Technology, Faculty of Applied Medical Sciences, Taibah University, Al-Madinah, Saudi Arabia; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia; 4Department of Medical Rehabilitation Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha, Aseer, Saudi Arabia; 5Medical City, King Khalid University, Abha, Aseer, Saudi Arabia; 6Medical Imaging Department, Aseer Central Hospital, Ministry of Health, Abha, Saudi ArabiaCorrespondence: Mohamed AdamDepartment of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Aseer, Saudi ArabiaEmail o_maurie2006@yahoo.comBackground: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown promising safety and acceptability. However, COVID-19 vaccine side effects play an essential role in public vaccine confidence. We aimed to study the side effects of these COVID-19 vaccines.Methods: A randomized, cross-sectional descriptive study was conducted between March and May of 2021. In total, 330 participants among the King Khalid University community in the Aseer region of the Kingdom of Saudi Arabia reported their side effects following the COVID-19 vaccine. A questionnaire was designed and validated to collect the participants’ demographic data and COVID-19-related symptoms after COVID-19 vaccine injection.Results: Symptoms associated with COVID-19 were reported by 226 participants (68.5%). The most common side effects reported by the participants were fever (n = 136, 41.2%), fatigue (n = 119, 36.1%), headache (n = 86, 24.2%), malaise (n = 121, 36.7%), myalgia (n = 121, 36.7%), and muscle and joint pain (n = 76, 23%). Of the participants, 5.1% became infected with COVID-19 after vaccination. Symptoms were significantly more common in males than in females (p = 0.006).Conclusion: The incidence of COVID-19 vaccination side effects in the Aseer region, Kingdom of Saudi Arabia, was consistent with the manufacturers’ data. The most common post-vaccination symptoms reported by the participants were fever, myalgia, malaise, fatigue, muscle and joint pain, and headache. The results of this study showed significant variation in adverse events between Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines. Healthcare providers and recipients of vaccines can be more confident about the safety of Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines.Keywords: COVID-19, vaccines, side effects, symptoms, Pfizer-BioNTech, Oxford-AstraZeneca

Mohamed Adam,1 Moawia Gameraddin,2 Magbool Alelyani,1 Gaffar Sarwar Zaman,3 Alamin Musa,1 Irshad Ahmad,4 Mohammad Y Alshahrani,3 Kamal Alsultan,2 Awadia Gareeballah2 1Department of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Asir, Kingdom of Saudi Arabia; 2Department of Diagnostic Radiologic Technology, Faculty of Applied Medical Sciences, Taibah University, Al-Madinah, Medina, Kingdom of Saudi Arabia; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Asir, Kingdom of Saudi Arabia; 4Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Asir, Kingdom of Saudi ArabiaCorrespondence: Mohamed AdamDepartment of Radiological Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Asir, Kingdom of Saudi ArabiaTel: +966 71248220Email o_maurie2006@yahoo.comBackground and Objective: The Kingdom of Saudi Arabia has exerted great efforts to prevent the spread of COVID-19. This research aims to scrutinize the outlook, awareness, and customs of Saudi undergraduate students regarding COVID-19.Methods: The current cross-sectional study comprises 178 undergraduate students in the Faculty of Applied Medical Sciences. The data were collected from online Google form questionnaires. The differences were picked out of the questionnaires, and the mean scores of the differences were duly assessed. The variables associated with knowledge, attitude, and practice toward COVID-19 were evaluated; moreover, a comparative study was conducted on these variables in different faculty departments. ANOVA, Student’s t-test, and binary logistic regression analysis were used to assess the data on knowledge, attitude, and practice.Results: Most of the undergraduate students were well acquainted with COVID-19. We obtained the mean knowledge score for COVID-19 to be 3.08 ± .82 (range: 1– 5), indicating good knowledge. The attitude means the score was 3.02 ± .61 (range: 0– 4), implying good positive attitudes. On assessing the mean score of practices, it was found 5 ± .47 (range: 0– 7), pointing towards perfect practices. There were no significant differences between males and females regarding knowledge, attitudes, and practice toward COVID-19 (p-value < 0.05).Conclusion: Students of Applied Medical Sciences are knowledgeable about COVID-19. Health education programs should be focused on protection and safety from COVID-19 for Applied Medical Sciences students, especially Medical Rehabilitation Sciences and Radiology. Hand hygiene awareness programs must be conducted for undergraduate students. Infection control should be part of the undergraduate applied for medical sciences curriculum program.Keywords: knowledge, attitude, practice, COVID-19, students

Mohammed Alfaifi,1,* Amit Kumar Verma,2,* Mohammad Yahya Alshahrani,1 Prakash C Joshi,2 Ali G Alkhathami,1 Irfan Ahmad,1 Abdulrahim Refdan Hakami,1 Mirza Masroor Ali Beg3,4 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; 2Department of Zoology and Environmental Sciences, GKV, Haridwar, India; 3Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, India; 4Department of Biochemistry, Maulana Azad Medical College, New Delhi, India*These authors contributed equally to this workCorrespondence: Mirza Masroor Ali BegDepartment of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, IndiaTel +917827655616Email mirzamasroor1986@gmail.comBackground: Type 2 diabetes mellitus [T2DM] has been one of the common diseases and is characterized by increased blood glucose levels and suggested that cell-free non-coding RNAs and microRNAs (miRNAs) have been demonstrated to serve as important diagnostic/prognostic biomarkers in diabetes.Materials/Methods: The present study included clinically confirmed newly diagnosed 200 cases of T2DM and 200 healthy subjects, and all the parameters were taken care in diagnosis. Blood samples collected in plain vials were used for cell-free total RNA extraction and after that 100ng of total RNA was used to synthesize the cDNA for cell-free lncRNA H19, miRNA-29a, and miRNA-29b expression using quantitative real-time PCR method. Serum Biochemical parameters were analyzed after collection of the sample to observe the changes among T2DM cases and healthy controls.Results: It was observed that type 2 diabetic patients had decreased [0.59 fold] lncRNA H19 expression while increased miRNA-29a [5.62 fold] and miRNA-29b [5.58 fold] expression. Decreased expression of lncRNA H19 was observed to be associated with gender [p=0.004], hypertension [p< 0.0001], weight loss [p=0.02] and fatigue [p=0.02]. Increased miRNA29a expression was linked with hypertension [p< 0.0001], alcoholism [p=0.04], and smoking [p< 0.0001] as well as miRNA-29b expression was associated with hypertension [p=0.0001], weight loss [p=0.002], smoking [p=0.0002], alcoholism [p< 0.0001]. Low [≤ 1 fold] and high [> 1 fold] expression of lncRNA H19 expression was linked with miRNA-29a [p=0.005] and miRNA-29b [p< 0.0001] expression. lncRNA H19 expression showed negative correlation with miRNA-29a expression [r= − 27, p< 0.0001] and miRNA-29b [r= − 47, p< 0.0001].Conclusion: The present study concluded that lower lncRNA H19 expression, and increased miRNA-29b, a miRNA-29b expression associated with the severity of T2DM patients. Decreased lncRNA H19 expression, and increased miRNA-29b, miRNA-29b expression observed to be interrelated with clinicopathological findings of T2DM patients could involve in pathogenesis disease.Keywords: diabetes, lncRNA, microRNA, gene expression, cell-free system

Aim: To correlate hematological, inflammatory indicators and serological responses among COVID-19 patients to point out the significant biomarkers for disease management and prognosis. Materials & methods: Standard analytical and molecular methods were used to assess various inflammatory and serological Responses among COVID-19 patients (ICU- (n = 99) and non-ICU patients (n = 64) as compared with health control (n = 40). Results: Significant differences in the Hb, WBC, Lymphocyte count, CRP and serum ferritin ( p  < 0.05) were observed. Patients' IgM/IgG antibodies against SARS-CoV-2 were associated with increased CRP, LDH and serum ferritin levels. Conclusion: A significant association between serum IgG/IgM and ICU admission was observed. Although serum ferritin and LDH can offer information about the extent of inflammation, they are exclusive factors for ICU admission.

Diabetes is a known inducer of hepatic ultrastructural alterations, and the expression of the immune biomarker that involves in T-cell immunity, cluster of differentiation 86 (CD86) is increased in diabetic patients with liver cirrhosis. The antidiabetic drug metformin has not previously been used to protect against type 2 diabetes mellitus (T2DM)-induced alternations in hepatic ultrastructure and the induction of the hepatic CD86/inflammation axis in diabetic animal models induced by streptozotocin and a high fat diet. To test our hypotheses, T2DM was induced in rats (model group) and the protective animals were treated with the antidiabetic drug metformin (200 mg/kg) until being sacrificed at week 12. A profound ultrastructural damage to the hepatocytes and liver tissue injury was induced by T2DM as demonstrated by hepatocytes with dark shrunken irregular nuclei, rarefied cytoplasm with lipid droplets, mitochondria with disrupted cristae, as well as depletion of glycogen granules and damaged of liver architecture, which were effectively ( p  < .0001) protected with metformin. Metformin also suppressed diabetes-induced hepatic gene expression of CD86 and inflammation as well as glycemia and liver injury markers. Furthermore, a significant correlation between hepatocyte damage and CD86, inflammation, glycemia, and biomarkers of liver injury was observed. These findings demonstrate that diabetes is associated with the induction of the hepatic CD86/inflammation axis and hepatocyte ultrastructural alterations while being protected by metformin.

This study provides an in-depth analysis of the pathogenic relevance, therapeutic implications, and mechanisms of treatment resistance associated with TLR4 and its ncRNAs in cancer immunopathogenesis. TLR4, a pivotal component of the innate immune response, has been implicated in promoting inflammation, tumorigenesis, and immune evasion across various malignancies, including gastric, ovarian, and hepatocellular carcinoma. The interactions between TLR4 and specific ncRNAs, such as lncRNAs and miRNAs, play a crucial role in modulating TLR4 signaling pathways, influencing immune cell dynamics, and contributing to chemoresistance. These ncRNAs facilitate tumor-promoting processes, including macrophage polarization, dendritic cell suppression, and T-cell regulation, effectively establishing an immunosuppressive tumor microenvironment that further enhances therapeutic resistance. A comprehensive understanding of the complex interplay between TLR4 and ncRNAs unveils potential avenues for identifying predictive biomarkers and discovering novel therapeutic targets in cancer. Future research initiatives should prioritize the development of personalized therapeutic strategies that specifically target TLR4 signaling and its ncRNA regulators to counteract drug resistance and improve clinical outcomes. This review extensively evaluates the role of TLR4 in cancer biology, emphasizing its critical importance in developing innovative cancer management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Alcaligenes faecalis is a Gram-negative, rod-shaped bacterium that is common in the environment and has been reported to have various bioactive metabolites of industrial potential applications, including antifungal, antibacterial, antimycobacterial, antiparasitic, anticancer, antioxidant activities. In this review, we highlighted and discussed the respective metabolites, pointing out their chemical diversities, purification, current challenges, and future directions. A. faecalis has an industrial role in biodegradation, biosurfactants, and different enzyme production. In this review, the up-to-date various Response Surface Methodology methods (RSM) that can be employed for statistical optimization of the bioactive secondary metabolites have been discussed and highlighted, pointing out the optimal use of each method, current challenges, and future directions.

This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) A. baumannii clinical isolates. A total of 43 CR- A. baumannii were isolated of which 37 (86.6 %) and 28 (65 %) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1 % and 72.1 % of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4 % (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100 % and 91.4 % of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring aph-3', bla oxa-58, bla GIM3 and bla CTX-M3 and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring bla GIM3 gene in Egypt., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The ongoing global health crisis caused by multidrug-resistant (MDR) bacteria necessitates quick interventions to introduce new management strategies for MDR-associated infections and antimicrobial agents' resistance. Phage therapy emerges as an antibiotic substitute for its high specificity, efficacy, and safety profiles in treating MDR-associated infections. Various in vitro and in vivo studies denoted their eminent bactericidal and anti-biofilm potential. This review addresses the latest developments in phage therapy regarding their attack strategies, formulations, and administration routes. It additionally discusses and elaborates on the status of phage therapy undergoing clinical trials, and the challenges encountered in their usage, and explores prospects in phage therapy research and application.

Natural killer (NK) cells are vital innate immune cells that play a crucial role in cancer therapy. They are targeted by therapies designed to modulate, retain, and enhance their antitumor function in vivo. In addition to whole-cell therapy, NK cell-derived exosomes (NDEs) offer high immune safety and are easily subject to chemical, biological, and immunological modifications. This makes them suitable for use in combination with various current cancer therapies to enhance efficacy, treatment outcomes, and reduce side effects in vivo. This review aims to outline summarizes the antitumor potential of NK cells, as well as the current challenges and opportunities in NK cell-based immunotherapies such as allogeneic and autologous NK cell transplantation, CAR NK cell therapy, and the use of cytokines and monoclonal antibodies. The review also explores the dual regulatory effects of tumor exosomes on NK cells, and highlights the potential of NDEs, either alone or in combination with other antitumor therapies, to reprogram the immunosuppressive tumor microenvironment and expedite the therapeutic effects of cancer immunotherapy in future clinical research., (© 2024 Wiley Periodicals LLC.)

Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions., Competing Interests: Declaration of competing interest I have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chemotherapy is a key treatment option for gastric cancer, but over 50% of patients develop either inherent or acquired resistance to these drugs, resulting in a 5-year survival rate of only about 20%. The primary treatment for advanced gastric cancer typically involves chemotherapy based on platinum or fluorouracil. Several factors can contribute to platinum resistance, including decreased drug uptake, increased drug efflux or metabolism, enhanced DNA repair, activation of pro-survival pathways, and inhibition of pro-apoptotic pathways. In recent years, there has been significant progress in biology aimed at finding innovative and more effective methods to overcome chemotherapy resistance. Small interfering RNAs (siRNAs) have emerged as a significant advancement in gene expression regulation, showing promise in enhancing the sensitivity of gastric cancer cells to chemotherapy drugs. However, siRNA therapies still face major challenges, particularly in terms of stability and efficient delivery in vivo. This article discusses the advances in siRNA therapy and its potential role in overcoming resistance to chemotherapeutic drugs such as cisplatin, 5-FU, doxorubicin, and paclitaxel in the treatment of gastric cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

MicroRNAs (miRNAs) are conserved non-protein-coding RNAs that are naturally present in organisms and can control gene expression by suppressing the translation of mRNA or causing the degradation of mRNA. MicroRNAs are highly concentrated in the PI3K/AKT pathway, and abnormal activation of the PI3K/AKT pathway plays a role in cancer progression. The AKT/PI3K pathway is critical for cellular functions and can be stimulated by cytokines and in normal situations. It is involved in regulating various intracellular signal transduction, including development, differentiation, transcriptional regulation, protein, and synthesis. There is a growing body of evidence indicating that miRNAs, which are abundant in exosomes released by different cells, can control cellular biological activities via modulating the PI3K/AKT pathway, hence influencing cancer progression and drug resistance. This article provides an overview of the latest research progress regarding the function and medical use of the PI3K/AKT pathway and exosomal miRNA/AKT/PI3K axis in the behaviors of cancer cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study investigated the impact of utilizing Rumex nepalensis leaf powder (RNL) as a phytogenic feed additive on performance, blood markers, intestinal microbiology and histomorphology in broiler chicken. One hundred eighty day-old Cobb broiler chicks were randomly divided into four treatment groups having three replicates with fifteen birds each. Four iso-caloric and iso-nitrogenous diets primarily based on maize-soybean were formulated, viz., CN (Control)-fed basal diet only; RNL 2.5 (basal diet + 2.5 g/kg RNL); RNL 5 (basal diet + 5 g/kg RNL); and RNL 10 (basal diet + 10 g/kg RNL). The results revealed a significant ( p < 0.05) increase in body weight gain and feed conversion ratio in dietary treatments compared to CN with best values in RNL 10 followed by RNL 5 . The blood markers like glucose, total protein, creatinine, alanine transaminase (ALT) and aspartate transaminase (AST) showed no significance ( p > 0.05) among all the treatments, however total cholesterol significantly ( p < 0.05) decreased in RNL 5 and RNL 10 as against CN. Regarding immune parameters, immunoglobulin G (IgG) and immunoglobulin M (IgM) levels significantly ( p < 0.05) enhanced in RNL 5 and RNL 10 . Antioxidant enzyme status showed that superoxide dismutase (SOD) increased and malondialdehyde (MDA) decreased significantly ( p < 0.05) in RNL 10 compared to CN. Gut health in terms of cecal microbiology and histomorphology of duodenum and jejunum were altered by inclusion of RNL in the broiler diet. A significant decrease ( p < 0.05) in coliform count was recorded by incorporation of dietary treatments with highest reduction in RNL 10 . Lactobacillus count and total viable count did not vary significantly ( p > 0.05) among dietary treatments and CN. Duodenal and jejunal villus height and villus height/crypt depth ratio were significantly ( p < 0.05) increased in RNL 5 and RNL 10 compared to RNL 2.5 and CN. Thus, it could be concluded that inclusion of Rumex nepalensis leaf powder in the diet resulted in improved performance and better immuno-antioxidant status of broilers. Further, an improvement in the gut health was observed in terms of positive effects on cecal microbiota and intestinal histomorphology of broiler chickens.

Emerging antibiotic resistance in bacteria threatens immune efficacy and increases susceptibility to bone degradation and arthritic disorders. In our current study, we utilized a three-layer in-silico screening approach, employing quantum chemical methods, molecular docking, and molecular dynamic methods to explore the novel drug candidates similar in structure to floroquinolone (ciprofloxacin). We investigated the interaction of novel similar compounds of ciprofloxacin with both a bacterial protein S. aureus TyrRS (1JIJ) and a protein associated with gout arthritis Neutrophil collagenase (3DPE). UTIs and gout are interconnected through the elevation of uric acid levels. We aimed to identify compounds with dual functionality: antibacterial activity against UTIs and antirheumatic properties. Our screening based on several methods, sorted out six promising ligands. Four of these (L1, L2, L3, and L6) demonstrated favorable hydrogen bonding with both proteins and were selected for further analysis. These ligands showed binding affinities of -8.3 to -9.1 kcal/mol with both proteins, indicating strong interaction potential. Notably, L6 exhibited highest binding energies of -9.10 and -9.01 kcal/mol with S. aureus TyrRS and Neutrophil collagenase respectively. Additionally, the pkCSM online database conducted ADMET analysis on all lead ligand suggested that L6 might exhibit the highest intestinal absorption and justified total clearance rate. Moreover, L6 showed a best predicted inhibition constant with both proteins. The average RMSF values for all complex systems, namely L1, L2, L3 and L6 are 0.43 Å, 0.57 Å, 0.55 Å, and 0.51 Å, respectively where the ligand residues show maximum stability. The smaller energy gap of 3.85 eV between the HOMO and LUMO of the optimized molecule L1 and L6 suggests that these are biologically active compound. All the selected four drugs show considerable stabilization energy ranging from 44.78 to 103.87 kcal/mol, which means all four compounds are chemically and physically stable. Overall, this research opens exciting avenues for the development of new therapeutic agents with dual functionalities for antibacterial and antiarthritic drug designing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rice (Oryza sativa) is a staple food for billions of people across the globe, that feeds nearly three-quarters of the human population on Earth, particularly in Asian countries. Rice yield has been drastically reduced and severely affected by various biotic and abiotic stresses, especially pathogens. Controlling the attack of such pathogens is a matter of immediate concern as yield losses in rice crops could deprive millions of lives of nourishment worldwide. Pyricularia oryzae is one such pathogen that has been considered the major disease of rice because of its worldwide geographic distribution. P. oryzae belongs to the kingdom fungi, that causes rice blast ultimately adversely affecting the yield of the rice crop. Keeping in view this alarming scenario, the present study was designed so that the identifications of genome-encoded miRNAs of Oryza sativa were employed to target and silence the genome of P. oryzae. This study accomplished the computational analysis of algorithms related to miRNA target prediction. Four computational target prediction algorithms i.e., psRNATarget, RNA22, miRanda, and RNAhybrid were utilized in this investigation. The consensus among target prediction algorithms was created to discover six miRNAs from the O. sativa genome with the conservation of the target site fully evaluated on the genome of P. oryzae. The discovery of these novel six miRNAs in Oryza sativa paved a strong way toward the control of this disease in rice. It will open doors for further research in the field of gene silencing in rice. These miRNAs can be designed and employed in the future as experimentation to create constructs regarding the silencing of P. oryzae in rice crops. In the future, this research would be surely helpful for the development of P. oryzae resistant rice varieties., (© 2024. The Author(s).)

With the current spread of clinically relevant multidrug-resistant (MDR) pathogens, insufficient unearthing of new anti-infectives, and the high cost required for approval of new antimicrobial agents, a strong need for getting these agents via more economic and other alternative routes has emerged. With the discovery of the biosynthetic pathways of various antibiotics pointing out the role of each gene/protein in their antibiotic-producing strains, it became apparent that the biosynthetic gene clusters can be manipulated to produce modified antibiotics. This new approach is known as the combinatorial biosynthesis of new antibiotics which can be employed for obtaining novel derivatives of these valuable antibiotics using genetically modified antibiotic-producing strains (pathway engineering). In this review and based on the available biosynthetic gene clusters of the major aminoglycoside antibiotics (AGAs), the possible alterations or modifications that could be done by co-expression of certain gene(s) previously known to be involved in unique biosynthetic steps have been discussed. In this review defined novel examples of modified AGA using this approach were described and the information provided will act as a platform of researchers to get and develop new antibiotics by the antibiotic-producing bacterial strains such as Streptomyces, Micromonospora,…etc. This way, novel antibiotics with new biological activities could be isolated and used in the treatment of infectious diseases conferring resistance to existing antibiotics., (© 2024. The Author(s).)

Istamycins (ISMs) are 2-deoxyfortamine-containing aminoglycoside antibiotics (AGAs) produced by Streptomyces tenjimariensis ATCC 31603 with broad-spectrum bactericidal activities against most of the clinically relevant pathogens. Therefore, this study aimed to statistically optimize the environmental conditions affecting ISMs production using the central composite design (CCD). Both the effect of culture media composition and incubation time and agitation rate were studied as one factor at the time (OFAT). The results showed that both the aminoglycoside production medium and the protoplast regeneration medium gave the highest specific productivity. Results also showed that 6 days incubation time and 200 rpm agitation were optimum for their production. A CCD quadratic model of 17 runs was employed to test three key variables: initial pH, incubation temperature, and concentration of calcium carbonate. A significant statistical model was obtained including, an initial pH of 6.38, incubation temperature of 30 ˚C, and 5.3% CaCO 3 concentration. This model was verified experimentally in the lab and resulted in a 31-fold increase as compared to the unoptimized conditions and a threefold increase to that generated by using the optimized culture media. To our knowledge, this is the first report about studying environmental conditions affecting ISM production as OFAT and through CCD design of the response surface methodology (RSM) employed for statistical optimization. In conclusion, the CCD design is an effective tool for optimizing ISMs at the shake flask level. However, the optimized conditions generated using the CCD model in this study should be scaled up in a fermenter for industrial production of ISMs by S. tenjimariensis ATCC 31603 considering the studied environmental conditions that significantly influence the production proces., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antibiotic overuse in poultry feeds has disastrous implications; consequently, long-term alternatives must be developed. As a result, the current study aims to assess the impact of Aspergillus niger filtrate (ANF) high in organic acids grown on agro-industrial residue of faba bean (AIRFB) on quail diet, as well as their influence on bird productivity, digestion, carcass yield, blood chemistry, and intestinal microbiota. A total of 240 Japanese quails (aged 7 d) were used in this study, divided equally among 5 experimental groups with 48 quails each. Group 1 (G1) received a basal diet without any ANF, group 2 (G2) received a basal diet supplemented with 0.5 mL ANF/kg diet, group 3 (G3) received a basal diet supplemented with 1.0 mL ANF/kg diet, group 4 (G4) received a basal diet supplemented with 1.5 mL ANF/kg diet, and group 5 (G5) received a basal diet supplemented with 2 mL ANF/kg diet. The performance parameters were monitored at 1 to 3, 3 to 5, and 1 to 5 wk. Adding ANF increased body weight at 3 and 5 wk, as well as body weight gain at 1 to 3, 3 to 5, and 1 to 5 wk, compared to the control diet. The ANF fed quails had the highest feed conversion ratio compared to the control group. The addition of ANF to the quail diet had no effect on the weight of the carcass, gizzard, heart, liver, giblets, or dressing; however, it did lower triglycerides, low-density lipoprotein, and very low-density lipoprotein while increasing high-density lipoprotein levels. The quail groups that received ANF had enhanced immunological indices such as IgG, IgM, IgA, and lysozymes. It also increased the levels of superoxide dismutase and total antioxidant contents, as well as catalase, and digestive enzymes such as protease, amylase, and lipase. However, it lowered the blood MDA levels compared to control. It has been demonstrated that the total gut microbiota, Escherichia coli, total coliforms, and the population of Salmonella are all reduced in ANF-fed quails. Histological examination of ANF quails' liver and intestinal sections revealed normal hepatic parenchyma, typical leaf-like intestinal villi, and comparatively short and frequently free lumina. In conclusion, Japanese quail showed improvements in performance, digestive enzymes, antioxidant indices, immunity, and capacity to reduce intestinal pathogenic bacteria after consuming diet supplemented with ANF., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In remote areas, particularly in developing countries, there is a growing interest in off-grid solar PV systems for their ability to provide clean and affordable electricity. However, these systems often face limitations in powering essential amenities, including sports facilities, due to restricted capabilities and inadequate battery storage. To address these challenges and promote energy independence, this paper proposes an AI-enabled sports-system peer-to-peer (P2P) energy exchange network within the digital economy. This innovative system leverages AI to optimize energy distribution specifically for sports-related infrastructures, ensuring efficient use of solar power and improved energy availability for both recreational and community needs. The proposed P2P network operates on a three-part Internet of Things (IoT) framework, facilitating automatic energy sharing among interconnected systems. This approach not only enhances the performance of existing solar power setups but also ensures that energy demands for sports facilities are met effectively. Feasibility studies of this system reveal promising outcomes, including a 13.67% increase in community energy independence and a 12.20% reduction in overall energy consumption. The AI-powered sports-system network demonstrates its potential to support sustainable development and improve the quality of life in remote areas by integrating sports and energy needs within the digital economy context., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The Middle East has witnessed a greater spread of infectious Dengue viruses, with serotype 2 (DENV-2) being the most prevalent form. Through this work, multi-epitope peptide vaccines against DENV-2 that target E and nonstructural (NS1) proteins were generated through an immunoinformatic approach. MHC class I and II and LBL epitopes among NS1 and envelope E proteins sequences were predicted and their antigenicity, toxicity, and allergenicity were investigated. Studies of the population coverage denoted the high prevalence of NS1 and envelope-E epitopes among different countries where DENV-2 endemic. Further, both the CTL and HTL epitopes retrieved from NS1 epitopes exhibited high conservancies' percentages with other DENV serotypes (1, 3, and 4). Three vaccine constructs were created and the expected immune responses for the constructs were estimated using C-IMMSIM and HADDOCK (against TLR 2,3,4,5, and 7). Molecular dynamics simulation for vaccine construct 2 with TLR4 denoted high binding affinity and stability of the construct with the receptor which might foretell favorable in vivo interaction and immune responses., (© 2024. The Author(s).)

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, and fine-tuning T-cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC-Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident., (© 2024 John Wiley & Sons Ltd.)

The expression of the nuclear paraspeckle assembly transcript 1 (NEAT1), as a well-known long non-coding RNA (lncRNA), is often upregulated in varied types of cancers and associated with poor survival outcomes in patients suffering from tumors. NEAT1 promotes the tumors growth by influencing the various genes' expression profile that regulate various aspects of tumor cell behavior, in particular tumor growth, metastasis and drug resistance. This suggests that NEAT1 are capable of serving as a new diagnostic biomarker and target for therapeutic intervention. Through interrelation with enhancer of zeste homolog 2 (EZH2), NEAT1 acts as a scaffold RNA molecule, and thus regulating the expression EZH2-associated genes. Additionally, by perform as miRNA sponge, it constrains suppressing the interactions between miRNAs-mediated degradation of target mRNAs. In light of this, NEAT1 inhibition by small interfering RNA (siRNA) hampers tumorgenesis. We summarize recent findings about the expression, biological functions, and regulatory process of NEAT1 in human tumors. It specifically emphasizes the clinical significance of NEAT1 as a novel diagnostic biomarker and a promising therapeutic mark for many types of cancers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Furan is generated in a wide array of heat-treated foods through thermal degradation, leading to severe impairments in the male reproductive system. The main objective of this study was to investigate the potential of pomegranate peel extract (PGPE) in mitigating testicular dysfunctions induced by furan. Male rats were categorized into four groups: control/untreated, PGPE, furan, and PGPE + furan group. The study results revealed that furan-treated rats exhibited significantly elevated aminotransferase and phosphatase activity, and also generated increased oxidative stress, and reduced antioxidative stress protein activity. Additionally, protein content levels (ALT, AST, ALP, and ACP) and activities of steroidogenic Leydig cell hydroxysteroid dehydrogenase (3β-HSD and 17β-HSD) enzymes were significantly decreased. Significant variations in testicular parameters, apoptotic genes (Bcl-2, P53, and Caspase3), inflammatory and anti-inflammatory cytokines (IL1β, IL10), male sex hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sperm quality were also observed. Furthermore, testicular histological abnormalities were confirmed by biochemical and molecular modifications. Notably, PGPE pre-treated furan-intoxicated animals exhibited significant improvements in most of the assessed parameters compared to furan-treated groups. In conclusion, PGPE presents essential preventive measures and a novel pharmacological potential therapy against furan-induced testicular injury., Competing Interests: Declaration of competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Multidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate., Methods: Standard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate., Results: Out of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with β-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (β-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents., Conclusion: Fortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly., (© 2024. The Author(s).)

Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052., (© 2024. The Author(s).)

A total of 150 adult quails, aged 8 wk, were divided into 5 groups to study the effect of sumac seed powder on reproductive and productive parameters, egg quality, digestive enzymes, and quail breeders' blood profiles. Dietary supplements containing sumac powder were formulated as follows: group 1 (G1) (control, only basal diet); group 2 (G2) (basal diet + 1 g sumac powder/kg diet); group 3 (G3) (basal diet + 2 g sumac powder/kg diet); group 4 (G4) (basal diet + 3 g sumac powder/kg diet); and group 5 (G5) (basal diet + 4 g sumac powder/kg diet). The feed conversion ratio was significantly higher at all levels of sumac powder (P < 0.05) compared to the control group (G1). Overall, during the study (8-16 wk), quail-fed 3 g sumac powder/kg diet (G4) showed no significant increase (P > 0.05) in the feed intake compared to the control group. Sumac powder supplementation significantly (P < 0.05) increased egg number, egg weight, egg mass, fertility, and hatchability. While supplementing with sumac powder did not impact other egg quality parameters, it did significantly (P < 0.05) increase yolk percentage, Haugh unit, and unit surface shell weight. Furthermore, when compared to the control group (G1), birds given 2, 3, or 4 g of sumac powder/kg diet showed a significant improvement (P < 0.05) in hematological parameters such as red blood cells, white blood cells, and hemoglobin, as well as a decrease in glucose levels. Feeding quail with a 3 g sumac powder/kg diet (G4) resulted in significantly (P < 0.05) higher globulin levels and improved albumin/globulin ratio compared to other treatments and control (G1). Sumac powder intake significantly (P < 0.05) reduced plasma lipid profile, liver enzymes (aspartate aminotransferase, and alanine aminotransferase), and kidney functions (creatinine, and urea). Furthermore, the supplementation of sumac powder resulted in a substantial increase (P < 0.05) in the levels of amylase, lipase, and protease. Sumac powder administration also significantly (P < 0.05) improves immunity by boosting IgM, IgG, IgA, and lysozyme levels in quail breeders' plasma. Supplementing with sumac powder, on the other hand, increased levels of reduced glutathione, total antioxidant capacity, catalase, and superoxide dismutase. The results of the current study indicated that the addition of 1, 2, 3, and 4 g of sumac powder to the diet of Japanese quail breeders led to improvements in egg quality, digestive enzymes, reproductive and productive performances, and most blood hematological and biochemical parameters., Competing Interests: DISCLOSURES The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells. Genetic modification of these cells provides a dual approach to the treatment of AD and cancer. It can be used through both CAR-independent and CAR-dependent mechanisms. The use of CAR-based cell therapies has been successful in treating cancer patients, leading to further investigation of this innovative treatment for alternative diseases, including AD. The complementary roles of CAR T and CAR NK cells have stimulated exploration in this area. Our study examines the latest research on the therapeutic effectiveness of these cells in treating both cancer and ADs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Unlike simple molecular screening, a combined hybrid computational methodology has been applied which includes quantum chemical methods, molecular docking, and molecular dynamics simulations to design some novel ketonic derivatives. The current study contains the derivatives of an experimental ligand which are designed as a trade-off between drug likeness and inhibition strength. We investigate the interaction of various newly designed ketonic compounds with the breast cancer receptor known as the Estrogen Receptor Alpha (ERα). The molecular structures of all newly designed ligands were studied quantum chemically in terms of their fully optimized structures, 3-D molecular orbital distributions, global chemical descriptors, molecular electrostatic potentials and energies of frontier molecular orbitals (FMOs). All ligands under study show good binding affinities with the ERα protein. The ligands CMR2 and CMR4 exhibit improved molecular docking interactions. The intermolecular interactions indicate that CMR4 demonstrates better hydrophobic and hydrogen bonding interactions with protein (ERα). Furthermore, molecular dynamics simulations were conducted on ligands and reference drugs interacting with the ERα protein over a time span of 120 nanoseconds. The molecular dynamics results are interpreted in terms of ligand-protein stability and flexible behaviour based on their respective values of RMSD, RMSF, H-bonds, the radius of gyration, and SASA graphs. To analyse ligand-protein interactions throughout the entire 120 ns trajectory, a more advanced MM/PBSA method is utilized, where six selected ligands (CMR1, CMR2, CMR3, CMR4, CMR5 and CMR9) illustrate promising results for inhibition of the ERα receptor as assessed through MM/BBSA analysis. The CMR9 has the highest MM/BBSA binding free energy (-14.46 kcal/mol). The ADMET analysis reveals that CMR4 has maximum intestinal absorption (6.68) and clearance rate (0.1). All the compounds are non-toxic and safe to use. These findings indicate the potential of involving different computational techniques to design the ligand structures and to study the ligand-protein interactions for better understanding and achieving more potent synthetic inhibitors for breast cancer., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Atypical chemokine receptor 4 (ACKR4), also known as CCX-CKR, is a member of the chemokine receptor family that lacks typical G protein signaling activity. Instead, ACKR4 functions as a scavenger receptor that can bind and internalize a wide range of chemokines, influencing their availability and activity in the body. ACKR4 is involved in various physiological processes, such as immune cell trafficking and the development of thymus, spleen, and lymph nodes. Moreover, ACKR4 has been implicated in several pathological conditions, including cancer, heart and lung diseases. In cancer, ACKR4 plays a complex role, acting as a tumor suppressor or promoter depending on the type of cancer and the stage of the disease. For instance, ACKR4 may inhibit the growth and metastasis of breast cancer, but it may also promote the progression of hepatocellular carcinoma and gastric cancer. In inflammatory situations, ACKR4 has been found to modulate the recruitment and activation of immune cells, contributing to the pathogenesis of diseases such as myocardial infraction and pulmonary sarcoidosis. The study of ACKR4 is still ongoing, and further research is needed to fully understand its role in different physiological and pathological contexts. Nonetheless, ACKR4 represents a promising target for the development of novel therapeutic strategies for various diseases., (© 2024 John Wiley & Sons Ltd.)

Echinococcus granulosus is a zoonotic parasite infects many livestock species, especially cattle, sheep, goat and buffalo, causing cystic echinococcosis. The aim of this study was to demonstrate the presence of the parasite and parasitic tissue damage histopathologically and to determine the role of oxidative stress in the tissue damage through the immunohistochemical detection of the oxidative damage-marker malondialdehyde (MDA) and the antioxidant response-marker superoxide dismutase (SOD). The material of the study consisted of 20 liver samples with Echinococcus cysts and 10 E.granulosus- negative healthy liver samples obtained from different cattle at various times from slaughterhouses in Kırıkkale province, Turkey. Histopathologically, Echinococcus cysts of various sizes were observed along with the surrounding fibrous connective tissue. Giant cells, mononuclear cells, and eosinophilic leukocytes were found between the fibrous connective tissue and the cyst. In the parenchymal tissue distant from the cyst, inflammatory changes were observed, including vacuolation and necrosis in hepatocytes, congestion and dilation sinusoidal capillaries. Immunohistochemically, MDA immunopositivity was observed in both hepatocytes surrounding the cyst and areas distant from the cyst, while SOD immunopositivity was mainly detected in fibrous connective tissue and hepatocytes surrounding the Echinococcus cysts. A significant increase in MDA immunoreactivity was observed in E.granulosus s.l.-infected livers. Although no statistically significant change was observed in SOD immunopositivity in the liver tissues with cystic echinococcosis, regional variations were noted. Germinal layer (GL) of Echinococcus cyst showed immunopositive staining for MDA, while laminated layer (LL) exhibited immunonegative staining. To the authors' best understanding, this study represents a pioneering effort in showcasing and evaluating the immunoreactivities of MDA and SOD within the liver tissue afflicted with Echinococcus cysts. Simultaneously, the examination extends to encompass tissue damage and the infiltration of inflammatory cells. This study highlights the role of oxidative stress in the pathogenesis of Cystic Echinococcosis (CE) and the need for further investigation of antioxidant defense mechanisms and their regional variations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hepatic tumors present a formidable challenge in cancer therapeutics, necessitating the exploration of novel treatment strategies. In recent years, targeting the immune system has attracted interest to augment existing therapeutic efficacy. The immune system in hepatic tumors includes numerous cells with diverse actions. CD8+ T lymphocytes, T helper 1 (Th1) CD4+ T lymphocytes, alternative M1 macrophages, and natural killer (NK) cells provide the antitumor immunity. However, Foxp3+ regulatory CD4+ T cells (Tregs), M2-like tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) are the key immune inhibitor cells. Tumor stroma can also affect these interactions. Targeting these cells and their secreted molecules is intriguing for eliminating malignant cells. The current review provides a synopsis of the immune system components involved in hepatic tumor expansion and highlights the molecular and cellular pathways that can be targeted for therapeutic intervention. It also overviews the diverse range of drugs, natural products, immunotherapy drugs, and nanoparticles that have been investigated to manipulate immune responses and bolster antitumor immunity. The review also addresses the potential advantages and challenges associated with these approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

We developed a facile electroanalytical system for the rapid and sensitive detection of pyrimethanil through the modification of carbon paste electrode surface using the as-fabricated europium doped feather-type CuO nanoflowers (FT-Eu 3+ -CuO NF sensor). The peak current of pyrimethanil oxidation was elevated by the sensor due to the integration of appreciable electrochemical features of the modifier, which indicates the high ability of the modified electrode to enhance the sensitivity of pyrimethanil detection. The pyrimethanil sensor under the optimized setting had a broad linear dynamic range (0.001-800.0 μM) and a narrow limit of detection (0.18 nM). The practical applicability of the as-fabricated electrode was verified by sensing pyrimethanil in real samples; it also exhibited commendable specificity, stability and reproducibility.

The sugarcane industry often utilizes effluent for irrigation purposes; however, its intricate composition and elevated metal contaminants pose a potential risk of soil and crop contamination. Consequently, it is imperative to employ effective strategies to ensure the safe utilization of this resource for crop cultivation. One such strategy involves the dilution of sugarcane industry effluent. Dilution is a practical approach to mitigate its toxicity, minimizing its adverse impact on soil and crop health. That's why the current study explored the best dilution of sugarcane industrial effluent (SW) for cultivating canola varieties. A total of 15 canola varieties were cultivated 0%, 20%, 40%, 60%, 80%, and 100% SW. Results showed that 60% SW Faisalabad Canola and Punjab Canola improved germination, shoot length, root length, shoot fresh and dry weight, root fresh and dry weight, and chlorophyll contents compared to other treatments and control. AARI Canola and CON-III showed poor growth and chlorophyll contents under 60%SW. Dunkled and Oscar cultivars showed moderate improvement in growth and chlorophyll contents under 60SW. The 60% SW can be recommended for maximum growth benefits in canola cultivars, specifically Faisalabad Canola and Punjab Canola. At 20SW, the root dry weight of Faisalabad Canola increased by 2.7%, while Punjab Canola increased by 3.4%. Canola showed the highest increase in POD activity compared to the control, with a 55.45% increase, followed by Sandal Canola, with a 43.26% increase. However, additional field-level experiments are needed to determine the best cultivars suitable for optimal growth under 80SW and 60SW irrigation conditions., (© 2024. The Author(s).)

The ribosomal protein S6 kinase beta-1 (RPS6KB1), also known as p70S6 kinase, plays a crucial role in various disease-related conditions such as diabetes, obesity, and cancer. Its activity is regulated by phosphorylation events, including phosphorylation of Threonine 389 in the hydrophobic motif by the mammalian target of rapamycin complex 1 (mTORC1) and phosphorylation of Threonine 229 in the activation loop by PDK1 (phosphoinositide-dependent kinase 1). However, other phenomena connected to RPS6KB1 remain unknown. In this study, we employed virtual screening and molecular docking techniques on the molecules in the ZINC library to identify potential inhibitors. Molecular dynamics (MD) simulations and MMGBSA calculations were carried out on promising compounds to determine their binding affinity and stability. We also evaluated the drug-likeness properties of the selected compounds. A comparative study between the native RPS6KB1 structure, co-crystal ligands, and the shortlisted molecules from the ZINC dataset was carried out. The identified molecules possess significant potential for future in vitro and in vivo studies, paving the way for developing effective cancer treatments.Communicated by Ramaswamy H. Sarma.

Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1β) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1β activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1β inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1β target, and the top ten small molecules were selected based on their binding energy. The small molecule named 'ZINC08101049' was prioritized based on binding energy (-9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1β. Next, IL1β alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1β, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics.Communicated by Ramaswamy H. Sarma.

With the help of both theoretical as well as experimental research, in vitro binding research with CT-DNA (calf thymus) and BSA (bovine serum albumin) were carefully examined to figure out the chemotherapeutic and pharmacokinetic facets of the Erbium complex, which contains 1,10-phenanthroline (Phen). The binding characteristics and the mechanism of complex's interaction with DNA as well as the protein were determined utilizing fluorescence quenching method. Findings indicated that the complex's interaction with DNA via groove binding into DNA's minor grooves, with their binding constants falling within the 10 4 M -1 range. Furthermore, thermodynamic characteristics and the fluorescence emission of the tryptophan residues of the protein were obtained through fluorescence quenching studies at different temperatures. According to the results of the binding constants, the protein's interactions with the Er- complex were moderate, demonstrating that the compound may be transported effectively by the protein. Molecular docking results supported that of the experimental research. The HeLa and MCF-7 cancer cell lines, along with the normal human fibroblast cell line, were used in an MTT assay evaluation of the Er-complex cytotoxicity. The Er-complex displayed a selective inhibitory effect on the proliferation of different cancer cells.Communicated by Ramaswamy H. Sarma.

Leucine-rich repeat kinase 2 (LRRK2) is a promising drug target for the therapeutic management of Parkinson's disease (PD) and other neurodegenerative disorders. LRRK2 inhibitors have the potential to modulate neuroinflammation, reduce alpha-synuclein aggregation and improve motor symptoms in PD patients. Although LRRK2 inhibitors are still in the early stages of clinical development, the identification of potent and selective inhibitors through structure-guided approaches provides a promising avenue for the development of effective therapies for PD and other neurodegenerative disorders. In this study, natural compounds from the IMPPAT database were screened using a state-of-the-art computational virtual screening approach to identify potential inhibitors of LRRK2. We carried out a docking screening on a library of natural compounds and identified a few compounds with strong binding affinity, docking score and specificity towards LRRK2 as the top hits. These hits were then subjected to further analysis based on multiple parameters for the Pan-assay interference compounds and their physicochemical and pharmacokinetics evaluation followed by a detailed interaction analysis. After careful evaluation, one natural compound, Panicutine, was identified as a promising candidate for LRRK2 due to its significant affinity and specificity towards the LRRK2 binding pocket. Additionally, it exhibited drug-like properties with blood-brain barrier permeability as determined by ADMET properties. To gain a deeper understanding of the stability and conformational changes of the LRRK2-ligand complex, MD simulations were conducted for 100 nanoseconds under explicit solvent conditions followed by principal component analysis and free energy dynamics. The simulation results demonstrated that the LRRK2-Panicutine complex remained stable throughout the simulation trajectories. Based on these findings, it is concluded that Panicutine has the potential to act as a LRRK2 inhibitor against PD and other neurodegenerative disorders.Communicated by Ramaswamy H. Sarma.

Unpleasant side effects of standard inflammatory drugs urges search for novel therapeutic candidates. This study aims in identifying novel anti-inflammatory NF-κB inhibitor by high-throughput computational and in-vitro pre-clinical approaches. Lead candidate selection was conducted by the use of computational docking molecular-dynamic simulations. The RBL-2H3 cell line, derived from rat basophils, was used to evaluate the release of cytokines and degranulation. The study focused on the study of neutrophil elastase and its role in cellular motility. Flow cytometry was utilized to evaluate the activation of basophils and the expression of critical signaling proteins. High throughput screening identified CSB-0914 to stably bind NF-κB-p50 subunit. Dose based loss in T NF-α and IL-2 release were observed in RBL-2H3 cells in addition to degranulation inhibition by CSB-0914. The compound demonstrated significant efficacy in reducing basophil activation assay induced by FcεRI receptors, with an IC50 value of 98.41 nM.. A dose dependent decrease in neutrophil migration and elastase were observed when treated with CSB- 0914. The compound was effective in decreasing. Upon stimulation, RBL-2H3 cells exhibited phosphorylation of NF-κB p-65 as well as upregulation of the Nrf2 and HO-1 signaling pathways. Collectively, our study has successfully identified a novel inhibitor called CSB-0914 that effectively regulates inflammatory responses. These reactions are primarily mediated by the interplay between NF-κB, Nrf2, and HO-1. The findings of this study provide support for the need to conduct more research on CSB-0914 with the aim of its development as a pharmaceutical agent for anti-inflammatory purposes.Communicated by Ramaswamy H. Sarma.

Within the realm of soluble factors that have emerged as potential targets for therapeutic intervention, the chemokine interleukin-8 (IL-8) has garnered attention as a potential contributor to treatment responses in various cancer types. The utilization of naturally occurring anticancer compounds for treating cancer patients has shown substantial advancements in survival rates across early and advanced stages of the disease. In silico research findings provide support for the application of phytochemicals as potential inhibitors of IL-8, and phytochemicals exhibiting a high binding free energy and crucial interactions display promising anticancer properties, positioning them as candidates for future drug development. Noteworthy phytochemicals such as IMPHY006634 (Isohydnocarpin), IMPHY007957 (Chitranone) and IMPHY013015 (1-Hydroxyrutaecarpine) were predicted to possess inhibitory activity against IL-8, with calculated energies ranging from -9.9 to -9.1 kcal/mol, respectively. Several hydrogen bonds, including common amino acid residues Lys9 and CYS48, were identified. Molecular dynamics calculations conducted on these potent inhibitors demonstrated their stability throughout a 200 ns simulation, as indicated by metrics such as RMSD, RMSF, Rg, SASA, H-bonds, PCA and FEL analysis. Moreover, PASS analysis and adherence of these natural compounds to drug-likeness rules like Lipinski's further strengthen their candidacy. Considering these calculations and various parameters, these three prominent natural compounds emerge as promising candidates for anti-IL-8 therapy in the management of cancer.Communicated by Ramaswamy H. Sarma.

Breast cancer (BC) is a malignant neoplasm that begins in the breast tissue. After skin cancer, BC is the second most common type of cancer in women. At the end of 2040, the number of newly diagnosed BC cases is projected to increase by over 40%, reaching approximately 3 million worldwide annually. The hormonal and chemotherapeutic approaches based on conventional formulations have inappropriate therapeutic effects and suboptimal pharmacokinetic responses with nonspecific targeting actions. To overcome such issues, the use of nanomedicines, including liposomes, nanoparticles, micelles, hybrid nanoparticles, etc., has gained wider attention in the treatment of BC. Smaller dimensional nanomedicine (especially 50-200 nm) exhibited improved in vivo effectiveness, such as better tissue penetration and more effective tumor suppression through enhanced retention and permeation, as well as active targeting of the drug. Additionally, nanotechnology, which further extended and developed theranostic nanomedicine by incorporating diagnostic and imaging agents in one platform, has been applied to BC. Furthermore, hybrid and theranostic nanomedicine has also been explored for gene delivery as anticancer therapeutics in BC. Moreover, the nanocarriers' size, shape, surface charge, chemical compositions, and surface area play an important role in the nanocarriers' stability, cellular absorption, cytotoxicity, cellular uptake, and toxicity. Additionally, nanomedicine clinical translation for managing BC remains a slow process. However, a few cases are being used clinically, and their progress with the current challenges is addressed in this Review. Therefore, this Review extensively discusses recent advancements in nanomedicine and its clinical challenges in BC., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Fungal infections currently pose a real threat to human lives. In the current study, soil bacterial isolates were screened for the production of antifungal compounds to combat human fungal pathogens. Notably, the bacterial F1 isolate exhibited antimycotic action towards the Candida albicans ATCC 10231 and Aspergillus niger clinical isolates. By employing phenotypic and molecular techniques, we identified the F1 isolate as the Bacillus toyonensis isolate OQ071612. The purified extract showed stability within a pH range of 6-7 and at temperatures of up to 50 °C. It demonstrated potential antifungal activity in the presence of various surfactants, detergents, and enzymes. The purified extract was identified as 6-methoxy-1H-Indole-2-carboxylic acid using advanced spectroscopic techniques. To optimize the antifungal metabolite production, we utilized response surface methodology (RSM) with a face-centered central composite design, considering nutritional and environmental variables. The optimal conditions were as follows: starch (5 g/L), peptone (5 g/L), agitation rate of 150 rpm, pH 6, and 40 °C temperature. A confirmatory experiment validated the accuracy of the optimization process, resulting in an approximately 3.49-fold increase in production. This is the first documented report on the production and characterization of 6-methoxy-1H-Indole-2-carboxylic acid (MICA) antifungal metabolite from Bacillus toyonensis.