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Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.

Background Ifosfamide (IFS) has potential complications such as nephropathy and hemorrhagic cystitis (HC). Although mesna can prevent IFS-induced cystitis by direct binding and neutralization of acrolein, HC symptoms have still been observed clinically in most of these cases. Celery is a powerful healing vegetable that has antioxidant, anti-inflammatory, and anticancer effects. The current study evaluated the synergistic effects of mesna and celery seed on IFS-induced HC in rabbits. Methods Twenty male rabbits (four groups) were administered distilled water, IFS, mesna, and mesna+celery seed cotherapy (MCC) for three weeks. The serum and urinary bladder of experimental rabbits underwent biochemical (TNF-α, MDA, iNOS, SOD, GPx, and CAT), histopathological and ultrastructural investigations to evaluate the structural changes of the urinary bladder (UB). Results IFS injection resulted in severe cystitis with a remarkable increase in the scale of hematuria, elevations of TNF-α, MDA, and iNOS activity, and reduced activity of SOD, GPx, and CAT antioxidants. Additionally, the structure of UB exhibited evident mucosal edema and ulceration. In contrast, the MCC regimen group revealed partial synergistic improvement of all mentioned parameters. Conclusion IFS induced cystitis by releasing acrolein, which exerted a significant role in the pathogenesis of HC. In contrast, the MCC intake partially ameliorated the UB damage through its antioxidant and anti-inflammatory effects., Graphical Abstract

Any variation in normal cellular function results in mitochondrial dysregulation that occurs in several diseases, including cancer. Such processes as oxidative stress, metabolism, signaling, and biogenesis play significant roles in cancer initiation and progression. Due to their central role in cellular metabolism, mitochondria are favorable therapeutic targets for the prevention and treatment of conditions like neurodegenerative diseases, diabetes, and cancer. Subcellular mitochondria-specific theranostic nanoformulations for simultaneous targeting, drug delivery, and imaging of these organelles are of immense interest in cancer therapy. It is a challenging task to cross multiple barriers to target mitochondria in diseased cells. To overcome these multiple barriers, several mitochondriotropic nanoformulations have been engineered for the transportation of mitochondria-specific drugs. These nanoformulations include liposomes, dendrimers, carbon nanotubes, polymeric nanoparticles (NPs), and inorganic NPs. These nanoformulations are made mitochondriotropic by conjugating them with moieties like dequalinium, Mito-Porter, triphenylphosphonium, and Mitochondria-penetrating peptides. Most of these nanoformulations are meticulously tailored to control their size, charge, shape, mitochondriotropic drug loading, and specific cell-membrane interactions. Recently, some novel mitochondria-selective antitumor compounds known as mitocans have shown high toxicity against cancer cells. These selective compounds form vicious oxidative stress and reactive oxygen species cycles within cancer cells and ultimately push them to cell death. Nanoformulations approved by the FDA and EMA for clinical applications in cancer patients include Doxil, NK105, and Abraxane. The novel use of these NPs still faces tremendous challenges and an immense amount of research is needed to understand the proper mechanisms of cancer progression and control by these NPs. Here in this review, we summarize current advancements and novel strategies of delivering different anticancer therapeutic agents to mitochondria with the help of various nanoformulations.

Diabetes is a chronic illness. Hyperglycemia is the characteristic of this disorder. Diabetes is a global crisis which affects the economy and health of all nations. Over the last decades, the number of individuals living with diabetes has significantly increased worldwide. Asia is a key epicenter of the emerging diabetes epidemic, with China and India the two nations having the highest number of diabetic people. Economic development, modernization, unhealthy diet, population aging, and sedentary lifestyles are the major factors responsible for the increasing diabetes epidemic. Diabetes is associated with several complications, and cardiovascular disease is the most important cause of morbidity and mortality among people with diabetes. These life-threatening problems can be prevented or delayed by proper management of diabetes. Lifestyle modification is an important factor to decrease the diabetes risk. The frequency of diabetic complications will rise if there is a lack of cost-effective and sustainable interventions. Hence, prevention of diabetes and its complications such as diabetic retinopathy and cardiovascular disease should be a crucial part of all future health-related public policies among all nations. This review summarizes current epidemiological aspects of diabetes in the world along with its complications, preventive measures, and treatment.

Human bodies encompass very important symbiotic and mutualistic relationships with tiny creatures known as microbiota. Trillions of these tiny creatures including protozoa, viruses, bacteria, and fungi are present in and on our bodies. They play important roles in various physiological mechanisms of our bodies. In return, our bodies provide them with the habitat and food necessary for their survival. In this review, we comprehend the gut microbial species present in various regions of the gut. We can get benefits from microbiota only if they are present in appropriate concentrations, as if their concentration is altered, it will lead to dysbiosis of microbiota which further contributes to various health ailments. The composition, diversity, and functionality of gut microbiota do not remain static throughout life as they keep on changing over time. In this review, we also reviewed the various biotic and abiotic factors influencing the quantity and quality of these microbiota. These factors serve a significant role in shaping the gut microbiota population.

Faris A Alrumaihi1Masood A Khan2Khaled S Allemailem1Mohammed A Alsahli1Ahmad Almatroudi1Hina Younus3Sultan A Alsuhaibani1Mohammad Algahtani4Arif Khan2 1Department of Medical Laboratories,College of Applied Medical Sciences,Qassim University, Buraydah, Saudi Arabia;2Department of Basic Health Sciences,College of Applied Medical Sciences,Qassim University, Buraydah, Saudi Arabia;3Interdisciplinary Biotechnology Unit,Aligarh Muslim University, Aligarh, India;4Department of Laboratory Medicine,Security Forces Hospital, Mecca, SaudiArabia Purpose: The plant Trigonella foenum-graecum, well-known as fenugreek, has been shownto control type-2 diabetes, the level of cholesterol, inflammation of wounds, disorders relatedto gastrointestinal tracts, and cancer as well. The present study aimed to evaluate the anticancerpotential of methanolic fenugreek seed extract (FSE) and its possible molecularmechanism of action in breast cancer cells.Methods: The anticancer potential of FSE was evaluated in MCF-7 and SK-BR3 breastcancer cells through various cellular assays after selecting the IC10, IC25, IC35, and IC50doses by the cell cytotoxicity assay. Furthermore, the oral acute toxicity of FSE wasexamined in mice, according to the guidelines of the Organization for Economic Cooperationand Development (OECD).Results: FSE exhibited dose-dependent cytotoxicity, as the IC50 was found to be 150 and 40μg/mL for MCF-7 and SK-BR3 breast cancer cells, respectively. The cytological observationsshowed the typical apoptotic morphology in both of the breast cancer cells upontreatment with FSE, as it inhibited the migration and adhesion, in a dose-dependent manner.The flow cytometry analysis revealed that FSE induced a significant shift from G2/M, andpolyploidy (>G) at higher concentrations that suggested the activation of p53-mediatedmitotic catastrophe, consequently leading to apoptosis. FSE induced a significant increasein the mitochondrial depolarization, ROS as well as a Bax/Bcl-2 ratio, and also exhibited themitochondrial associated p53 signaling pathway. The in vivo acute toxicity data revealed thatthe oral administration of FSE did not induce any toxic effect in mice.Conclusion: This study, for the first time, reports the mechanistic details of the anti-cancerpotential of FSE. It requires a detailed analysis to understand the effect of FSE to induce theapoptosis through the multiple signaling pathways at varying concentrations. The nontoxiceffect of FSE in mice suggests to utilize it safely for pharmaceutical formulations in differentcancer systems. Keywords: fenugreek seed extract, breast cancer cells, mitotic catastrophe, apoptosis, p53signaling, mitochondria-associated pathway, oral acute toxicity

Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the abnormal expression of ER and EGF2 in breast cancer cells. Therefore, the development of alternatives to paclitaxel is urgently needed to overcome challenges involving drug resistance. An increasing number of studies has revealed miRNAs as novel natural alternative substances that play a crucial role in regulating several physiological processes and have a close, adverse association with several diseases, including breast cancer. Due to the therapeutic potential of miRNA and paclitaxel in cancer research, the current review focuses on the differential roles of various miRNAs in breast cancer development and treatment. miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed. These strategies involve improving the cellular uptake and bioavailability and reducing the toxicity of free paclitaxel to achieve accumulation tumor site. Furthermore, a molecular docking study was performed to ascertain the enhanced anticancer activity of the nanoformulation of ANG1005 and Abraxane. An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2. Therefore, ANG1005 and Abraxane may be more suitable in the therapeutic management of breast cancer than the existing free paclitaxel. miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers.

Purpose Diallyl sulfide (DAS), one of the organo-sulfur secondary metabolites in garlic, has been shown to inhibit the proliferation of cancer cells. The present study aimed to evaluate the mechanism of DAS in the prevention of benzo[a]pyrene (BaP)-induced lung cancer in a murine model. Materials and methods The mice were exposed to 50 mg/kg of BaP twice a week for 4 weeks in order to induce lung carcinoma. Pretreatment of mice with DAS (100 mg/kg) was started 2 weeks before BaP exposure and further continued for 21 weeks. The effect of DAS and BaP was evaluated by studying various parameters in the serum and tissues of the treated or untreated BaP-exposed mice. Results The histopathological findings demonstrated that DAS prevented the progression of malignant lung cancer and metastasis in the liver. A significant drop was observed in BaP-induced tumor marker enzymes (ADA, AHH, γ-GT, LDH) in the serum of the mice treated with DAS. Moreover, DAS treatment resulted in the recovery of antioxidant enzymes, SOD and CAT, in BaP-exposed mice. The induction of apoptosis and the destruction of cellular ROS were detected in cancer cells from the mice pre-treated with DAS. The immunohistochemical analysis revealed the up-regulation of fatty acid synthase (FASN) in the lungs and liver tissues of BaP-exposed mice and the treatment with DAS inhibited FASN expression. Conclusion The findings of the present study indicated that DAS-induced apoptosis is strongly associated with the downregulation of FASN in tumor tissues. To the best of our knowledge, this is the first study that describes the role of FASN in BaP-induced lung carcinogenesis.

Introduction Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and its incidence, as well as mortality rate, is increasing globally. In this paper, the epidemiological analysis of CRC which includes colon cancer (CC) and rectum cancer (RC) is done among the Saudi Arabian population based on the registered cases in the Saudi cancer registry between 2006 and 2016. The study describes the crude incidence rates (CIRs) and age-standardized incidence rates (ASIRs) of colorectal cancer by year of diagnosis, age group, and administrative regions to explore the spread, distribution, trend, and factual state of the disease in Saudi Arabia. Methodology For statistical analysis of data, t-test, sex ratio, descriptive statistics, and Kruskal-Wallis were done using IBM Statistical Package for the Social Sciences version 20.0 (SPSS). A total of 7849 and 5164 of colorectal cancer and rectum cancer cases were reported from January 2006 to December 2016, respectively. Results Results displayed that CRC is more frequent in males than females and have a high mean number and percentage in the old age group (60-75 and above). Riyadh (for CC and RC), Makkah (CC), and Eastern Province (RC) showed the highest mean CIR and ASIR for males. The highest CIR sex ratio was calculated in Jouf and Madinah for CC whereas Qassim, Jazan, and Tabuk were calculated highest for RC. Highest ASIR sex ratio reported in Jouf (CC) and Tabuk (RC). Lowest CIR and ASIR among males were reported in Baha (CC) and northern region (RC). In females, the highest mean CIR and ASIR were reported in Riyadh (CC and RC) and Makkah (CC). Lowest CIR and ASIR among females were reported in Jazan in both CC and RC. Conclusion Regions of Eastern Province, Northern Region, and Jouf showed the most significant changes of CIRs and ASIRs for both cancers, whereas the least significant change was reported in Jazan from 2006 to 2016.

Introduction Schistosomiasis is an important neglected tropical disease (NTD) in several developing countries. Praziquantel is the principle and efficacious chemotherapeutic agent that has been used to treat schistosomiasis for decades. Unfortunately, emerging resistance to praziquantel with accompanying reduced efficacy is reported in some localities. Hence, genetic diversity among parasite populations is of significant interest in assessing the effects of selective pressure generated by praziquantel therapy that might result in encouraging the emergence of new genotypes that are either non-susceptible or drug-resistant. The present study aimed to investigate the genetic diversity of Schistosoma haematobium among human populations using the RAPD technique to help clarify disease epidemiology and transmission. Materials and methods S. haematobium eggs were isolated from 50 of 134 patients from four different localities in Qena Governorate, Upper Egypt. These patients complained of terminal hematuria and burning micturition. Samples were used for molecular analysis using RAPD-PCR primers (A02, A07, A09, A10). Results Twenty S. haematobium isolates (40%) were amplified using the selected RAPD primers. Amplification patterns of these isolates showed distinct variation in the size and number of amplified fragments, indicating high genetic variation among these isolates. Conclusion To the best of our knowledge, this study is the first to characterize the genetic diversity of S. haematobium in human populations in Upper Egypt. Future studies on a larger geographic scale involving many districts in Upper Egypt should be encouraged. Information from such a study would provide better insight into clonal lineages of S. haematobium in this endemic area. In turn, understanding transmission of the parasite may have a major role in establishing control strategies for urogenital schistosomiasis in Upper Egypt.

Background: Cancer is the leading cause of death worldwide and the current mode of cancer treatment causes side effects on normal cells and are still the key challenges in its’ treatment. However, natural products or active compounds of medicinal plants have shown to be safe, affordable, and effective in diseases cure. Methods: In this context, scientific studies evidence the health-promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory, and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed anti-neoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells,and inhibiting the initiation, migration, invasion, and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB, and oncogenes. Results: The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improves the efficacy of drugs which is evident by decrease resistance to drugs and regulation of various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus, TM, in combination with anti-cancer drugs, can be a good strategy in the management of various types of cancer. Conclusion: In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer-based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.

Introduction: Lung cancer is one of the leading causes of cancer-related deaths worldwide, including in Saudi Arabia. In the past few decades, the incidence and mortality has increased considerably among the Saudi population. The incidence of lung cancer has increased more than 3% in less than two decades. The current study focuses on analyzing the frequency of diagnosed lung cancer cases, age-standardized incidence rate (ASIR), and crude incidence rate (CIR) classified by year of diagnosis, age group, and different administrative regions of Saudi Arabia, based on the Saudi cancer registry (SCR) for the period of 10 years from 2006–2016. Methodology: The present study is a cohort study that focuses on the epidemiological analysis of lung cancer cases. The statistical analysis was performed by t-test, sex ratio, Kruskal–Wallis, and descriptive statistics through SPSS version 20.0. Results: A total of 4530 lung cancer cases were reported from January 2006 to December 2016. Among males, the ASIR range was reported as 1.2 to 12.3 per 100,000 cases in different regions of Saudi Arabia. Moreover, among females, the ASIR range was reported from 0.2 to 3.1 per 100,000 cases in different regions of Saudi Arabia. Additionally, the overall age-standardized incidence sex ratio was 3.2 per 100,000 cases. The incidence of lung cancer increased with age as 23% was reported in the age group of more than 75 years. Conclusions: The study concludes a rise in crude incidence rates and ASIR for lung cancer among Saudi population. Among males, the Eastern region had the highest overall ASIR followed by Tabuk region, and, among females, the highest overall ASIR was reported in the Eastern region followed by Riyadh and the Northern region.

The purpose of the study was to investigate the expressions of VEGF and pAkt protein, and to evaluate their clinicopathological implications in oral cancer. A total of 55 cases of oral squamous cel...

Hospital-acquired infections (HAI) reflect as a major global safety concern for both patients and health-care professionals. These infections could be in the form of cross-infection, endogenous infection and environmental Infection. Over 80% of these infections are related to devices’ utilization needed for patients’ life support. Methods show this is an observational and cross-sectional study, to identify the microorganism and determine the potential source of transmitting of hospital acquired infection by routine devices in adult ICU. The samples were collected using Amies transport media; three swabs were taken from the surfaces of indwelling urinary catheter, mechanical ventilation device and central venous catheter used from every twelve patients. The samples were cultured and analyzed by using microbiologic technique. Finally, all samples analyzed by MicroScan WalkAway 96 pulse. Results showing the most bacteria isolated are “Klebsiella pneumonia” (18.37%), “Acinetobacter baumannii” (11.48%), “Staphylococcus epidermidis” (4.59%), “Staphylococcus haemolyticus” (4.59%), “E. coli” (4.59%), “Serratia marcescens” (2.3%), “Pseudomonas luteola” (2.3%), “Kocurio kristinae” (2.3%) and “Photorhabdus luminscens” (2.3%). This study detects a high contamination of routine devices and resistant organisms. In the end it is recommended that effective infection control practices and effective strategies to control antibiotic-resistant bacteria should be applied.

Background:Cancer is a multi-factorial disease including alterations in the cell signalling pathways. Currently, several drugs are in use to treat cancer but such drugs show negative side effects on normal cells and cause severe toxicity.Methods:The current research is mainly focused on medicinal plants with potential therapeutic efficacy in the treatment of cancer without any adverse effects on normal cells. In this regard, garlic and its active compounds including diallyl sulfide, diallyl trisulfide, ajoene, and allicin have been established to suppress the growth of cancer and killing of cancer cells.Result:The review focuses on garlic and its active compounds chemopreventive effect through modulating various cell signalling pathways. Additionally, garlic and its active compound were established to induce cell cycle arrest at the G0/G1 phase and G2/M phases in cancer cells, increase the expression of tumor suppressor genes, inhibit the angiogenesis process, induction of apoptosis and modulation of various other genetic pathways.Conclusion:This review sketches the diverse chemopreventive activities of garlic and their active ingredients in the management of cancer mainly focusing on cell signalling pathways.

Leptospirosis is identified as an important reemerging zoonotic disease distributed worldwide, caused by Leptospira. This study was carried out to explore the genetic characterization and its phylogenetic analysis of circulating Leptospira species, among the Aligarh region of western Uttar Pradesh in India, utilizing secY gene-based nucleotide sequence. A total of 190 human samples were included in the study. Positive samples were identified by ELISA, MAT and PCR. MAT was carried out utilizing local circulating Leptospira serovars. Four positive samples including two MAT positive samples were subjected to DNA sequencing for further confirmation and phylogenetic tree was constructed. Out of the total of 190 samples, 24 patients were found positive by ELISA and 29 by PCR. Two samples were found reactive in MAT with L. interrogans serovars like hebdomadis and copenhageni. Phylogenetic analysis of four isolates based on partial secY gene nucleotide sequences revealed that species obtained from the Aligarh region clustered with the several published pathogenic Leptospira interrogans, while some of our isolates nucleotide sequences also clustered with the published sequence of intermediate and saprophytic Leptospira serovars like Leptospira inadai and Leptospira meyeri. This pilot study will help us to decipher the present scenario of circulating serovars of leptospira as well as to identify the nucleotide changes in secY gene, in this region.

Oxidative stress is linked with inflammation, diabetic complications, and advanced glycation end products formation. Intake of flavonoid-rich foods has been reported to have a beneficial effect on human health. The aim of this study was to verify the therapeutic potential of Phyllanthusemblica and Azadiractha indica against glycation and other oxidative stress-induced complications such as inflammation using in vitro study. Ethanol extracts of Phyllanthus emblica fruit pulp and dried leaf of Azadiractha indica were prepared to investigate in vitro anti-inflammatory and anti-glycating potentials. In a DPPH assay, the EC50 value of extract of P. emblica and A. indica was found to be 1532.36 ± 0.17 and 1380.61 ± 0.27 µg/mL, respectively. The FRAP value of P. emblica and A. indica extract was 86.6 and 32.12 µg ascorbic acid/100 mg dry weight of the extract. The maximum percentage of H2O2 scavenging activity was 71.30% and 67.38%, respectively. Extracts of P. emblica and A. indica showed maximum inhibition of heat-induced BSA denaturation by 62.42% and 53.00%, heat-induced denaturation of egg albumin, by 50.84%% and 44.31%, and heat-induced hemolysis by 54.44% and 50.21%. Both extracts (600 µg/mL) significantly reduced the browning, structural changes, aggregation, and AGEs formation. Our biophysical studies confirmed the AGEs formation was inhibiting the potential of extracts. Thus, our findings confirm that these extracts are a rich source of antioxidants and may be utilized to prevent the oxidative stress-induced destruction of biomolecules, glycation, and in the therapy of a variety of health problems, including inflammation. Further, a combination of extracts of P. emblica and A. indica may be extremely useful in preventing and treating health problems.

Cholera is a severe small intestine bacterial disease caused by consumption of water and food contaminated with Vibrio cholera. The disease causes watery diarrhea leading to severe dehydration and even death if left untreated. In the past few decades, V. cholerae has emerged as multidrug-resistant enteric pathogen due to its rapid ability to adapt in detrimental environmental conditions. This research study aimed to design inhibitors of a master virulence gene expression regulator, HapR. HapR is critical in regulating the expression of several set of V. cholera virulence genes, quorum-sensing circuits and biofilm formation. A blind docking strategy was employed to infer the natural binding tendency of diverse phytochemicals extracted from medicinal plants by exposing the whole HapR structure to the screening library. Scoring function criteria was applied to prioritize molecules with strong binding affinity (binding energy < -11 kcal/mol) and as such two compounds: Strychnogucine A and Galluflavanone were filtered. Both the compounds were found favourably binding to the conserved dimerization interface of HapR. One rare binding conformation of Strychnogucine A was noticed docked at the elongated cavity formed by α1, α4 and α6 (binding energy of -12.5 kcal/mol). The binding stability of both top leads at dimer interface and elongated cavity was further estimated using long run of molecular dynamics simulations, followed by MMGB/PBSA binding free energy calculations to define the dominance of different binding energies. In a nutshell, this study presents computational evidence on antibacterial potential of phytochemicals capable of directly targeting bacterial virulence and highlight their great capacity to be utilized in the future experimental studies to stop the evolution of antibiotic resistance evolution.

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.

Chronic kidney disease (CKD) is considered a major health problem, which poses a burden for health care systems worldwide. It has been estimated that 10% of the population worldwide have CKD, however, most of the cases are undiagnosed. If left untreated, CKD could lead to kidney failure, which highlights the importance of early diagnosis and treatment. Pyuria has been reported in CKD patients, and could be the result of several comorbidities, such as diabetes, or urinary tract infections (UTIs). A few studies have shown that pyuria is associated with the late stages of CKD. However, there are limited data on the prevalence of non-UTI (sterile) and UTI–pyuria in different CKD patient populations, and its association with the decline in kidney function and progression of CKD. In this retrospective study, we report the prevalence of pyuria (sterile and UTI) in 754 CKD patients of King Fahd Specialist Hospital, Buraydah, Saudi Arabia. Our data showed that 164/754 CKD patients (21.8%) had pyuria, whereas 590 patients (78.2%) presented with no pyuria. There was a significantly higher percentage of late-stage (stage 4) CKD patients in the pyuric group compared to the non-pyuric group (36.6% vs. 11.9%). In line with the previous data, proteinuria was detected in a significantly higher percentage of pyuric patients, in addition to significantly higher levels of serum creatinine and urea, compared to non-pyuric patients. Furthermore, 13.4% of the pyuric CKD patients had UTI, whereas 86.6% presented with sterile pyuria. E. coli was indicated as the causative agent in 45.5% of UTI patients. Our patient data analysis showed that a significantly higher percentage of UTI–pyuric CKD patients, than sterile pyuric patients (63.6% vs. 19.7%), had higher numbers of urinary white blood cells (&gt, 50/HPF, WBCs). The data also showed that a higher percentage of UTI–pyuric patients were late-stage CKD patients, compared to sterile pyuric patients (50% vs. 34.5%). Our findings indicate that a high level of pyuria could be considered as a marker for late-stage CKD, and that UTI is an important risk factor for the decline in kidney function and the progression to late-stage CKD. We believe that further studies are needed to correlate pyuria to kidney function, which could be helpful in monitoring the progression of CKD. Moreover, the management of comorbidities, such as diabetes and UTIs, which are risk factors for CKD and associated pyuria, could help to control the progression of CKD to the late stages.

BackgroundAlthough COVID-19 is an acute disease that usually resolves rapidly in most cases, the disease can be fatal and has a mortality rate of about 1% to 56%. Alveolar injury and respiratory failure are the main causes of death in patients with COVID 19. In addition, the effect of the disease on other organs is not fully understood. Renal system affection has been reported in patients with COVID 19 and is associated with a higher rate of diverse outcomes, including mortality. Therefore, in the present work, we reported the clinical characteristics and laboratory data of hospitalized patients with COVID-19 and analyzed the manifestations that indicated renal system involvement and their impact on clinical outcomes.Materials and methodsThis was an observational retrospective study conducted at King Fahd Specialist Hospital, Buraydah, Saudi Arabia. All patients with COVID-19 who were admitted to this Hospital from April to December 2020 were included in the study. The patients’ findings at presentation were recorded. Demographic data and laboratory results (hematuria, proteinuria, urinary sediment cast and pus cell presence, and kidney function tests) were retrieved from electronic patient records.ResultsOne hundred and ninety-three patients with confirmed COVID 19 were included in the study. Dipstick examinations of all urine samples showed proteinuria and hematuria in 53.9% and 22.3% of patients, respectively, whereas microscopic examination revealed the presence of pus and brown muddy granular casts in 33.7% and 12.4% of samples, respectively. Acute kidney injury was reported in 23.3% of patients. A multivariable analysis demonstrated that hematuria was associated with acute kidney injury (AKI) (OR, 2.4; 95% CI, 1.2–4.9;P= 0.001), ICU admission (OR, 3.789; 95% CI, 1.913–7.505;P =0.003), and mortality (OR, 8.084; 95% CI, 3.756–17.397;P =0.002). Conversely, proteinuria was less significantly associated with the risk of AKI (OR, 1.56; 95% CI, 1.91–7.50;P =0.003), ICU admission (OR, 2.493; 95% CI, 1.25–4.72;P =0.001), and mortality (OR, 2.764; 95% CI, 1.368–5.121;P =0.003). Patients with AKI had a higher probability for mortality than did those without AKI (OR, 14.208; 95% CI, 6.434–31.375;P =0.003).ConclusionThe manifestations of the involvement of the renal system are not uncommon in COVID-19. These manifestations included proteinuria, hematuria, and AKI and were usually associated with a poor prognosis, including high incidences of both ICU admission and mortality.

Cryptococcus neoformans infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in the treatment of C. neoformans in cyclophosphamide injected leukopenic mice. A liposomal formulation of ellagic acid (Lip-EA) was prepared and characterized, and its antifungal activity was assessed in comparison to fluconazole (FLZ). The efficacy of the drug treatment was tested by assessing survival rate, fungal burden, and histological analysis in lung tissues. The safety of the drug formulations was tested by investigating hepatic, renal function, and antioxidant levels. The results of the present work demonstrated that Lip-EA, not FLZ, effectively eliminated C. neoformans infection in the leukopenic mice. Mice treated with Lip-EA (40 mg/kg) showed 70% survival rate and highly reduced fungal burden in their lung tissues, whereas the mice treated with FLZ (40 mg/kg) had 20% survival rate and greater fungal load in their lungs. Noteworthy, Lip-EA treatment alleviated cyclophosphamide-induced toxicity and restored hepatic and renal function parameters. Moreover, Lip-EA treatment restored the levels of superoxide dismutase and reduced glutathione and catalase in the lung tissues. The effect of FLZ or EA or Lip-EA against C. neoformans infection was assessed by the histological analysis of lung tissues. Lip-EA effectively reduced influx of inflammatory cells, thickening of alveolar walls, congestion, and hemorrhage. The findings of the present study suggest that Lip-EA may prove to be a promising therapeutic formulation against C. neoformans in immunocompromised persons.

With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-β, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.

Novel strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) causes mild to severe respiratory illness. The early symptoms may be fever, dry cough, sour throat, and difficulty in breathing which may lead to death in severe cases. Compared to previous outbreaks like SARS-CoV and Middle East Respiratory Syndrome (MERS), SARS-CoV2 disease (COVID-19) outbreak has been much distressing due to its high rate of infection but low infection fatality rate (IFR) with 1.4% around the world. World Health Organization (WHO) has declared (COVID-19) a pandemic on March 11, 2020. In the month of January 2020, the whole genome of SARS-CoV2 was sequenced which made work easy for researchers to develop diagnostic kits and to carry out drug repurposing to effectively alleviate the pandemic situation in the world. Now, it is important to understand why this virus has high rate of infectivity or is there any factor involved at the genome level which actually facilitates this virus infection globally? In this study, we have extensively analyzed the whole genomes of different coronaviruses infecting humans and animals in different geographical locations around the world. The main aim of the study is to identify the similarity and the mutational adaptation of the coronaviruses from different host and geographical locations to the SARS-CoV2 and provide a better strategy to understand the mutational rate for specific target-based drug designing. This study is focused to every annotation in a comparative manner which includes SNPs, repeat analysis with the different categorization of the short-sequence repeats and long-sequence repeats, different UTR's, transcriptional factors, and the predicted matured peptides with the specific length and positions on the genomes. The extensive analysis on SNPs revealed that Wuhan SARS-CoV2 and Indian SARS-CoV2 are having only eight SNPs. Collectively, phylogenetic analysis, repeat analysis, and the polymorphism revealed the genomic conserveness within the SARS-CoV2 and few other coronaviruses with very less mutational chances and the huge distance and mutations from the few other species.

Autophagy, a catabolic process, degrades damaged and defective cellular materials through lysosomes, thus working as a recycling mechanism of the cell. It is an evolutionarily conserved and highly regulated process that plays an important role in maintaining cellular homeostasis. Autophagy is constitutively active at the basal level; however, it gets enhanced to meet cellular needs in various stress conditions. The process involves various autophagy-related genes that ultimately lead to the degradation of targeted cytosolic substrates. Many factors modulate both upstream and downstream autophagy pathways like nutritional status, energy level, growth factors, hypoxic conditions, and localization of p53. Any problem in executing autophagy can lead to various pathological conditions including neurodegeneration, aging, and cancer. In cancer, autophagy plays a contradictory role; it inhibits the formation of tumors, whereas, during advanced stages, autophagy promotes tumor progression. Besides, autophagy protects the tumor from various therapies by providing recycled nutrition and energy to the tumor cells. Autophagy is stimulated by tumor suppressor proteins, whereas it gets inhibited by oncogenes. Due to its dynamic and dual role in the pathogenesis of cancer, autophagy provides promising opportunities in developing novel and effective cancer therapies along with managing chemoresistant cancers. In this article, we summarize different strategies that can modulate autophagy in cancer to overcome the major obstacle, i.e., resistance developed in cancer to anticancer therapies.

Background Prevalence of different respiratory allergies is increasing in the Kingdom of Saudi Arabia (KSA). Environmental risk factors of respiratory allergy vary regionally, hence the prevalence. This necessitates the needs for regional studies. This article reports prevalence and symptoms of respiratory allergies in the Qassim region, and the factors associated with the prevalence. Methods Eight hundred and fifty individuals aged ≥18 years and were living in the Qassim region filled up our structured online questionnaire between September and December 2020. We estimated the prevalence of different respiratory allergies with 95% confidence intervals. Multi-variable logistic regression analyses were performed to investigate the risk factors of respiratory allergies. Findings The prevalence of any respiratory allergy in the Qassim region was 28.8%. Most families (58.1%) had at least one member with respiratory allergy. The prevalence of allergic rhinitis and bronchial asthma were 13.5% and 11.2% 4.1% respectively. The reported symptoms included runny nose (13.6%), red, watery, and itchy eyes (10.4%), difficulty sleeping at night (10.2%), difficulty breathing in cold weather (9.2%), noisy breathing (8.5%), sneezing (8%), repeated coughing (7.5%) and shortness of breath (6.4%). Individuals with a family history were more likely to report any respiratory allergy (OR: 7.8), bronchial asthma (OR: 4.2) and allergic rhinitis (OR: 8.1) compared to the individuals without such family history. Odds of respiratory allergies was higher among males (OR: 1.5). Saudi nationals were less likely to report allergic rhinitis than the non-Saudis (OR: 0.4). Among those who reported a respiratory allergy, most (73.5%) received treatment and majority (61.7%) demonstrated compliance to the treatment, 8.8% needed hospitalization, and 23.1% needed emergency nebulization. Conclusions Prevalence reported in our study is different than that reported in other regions. Variability in the environmental exposures might explain this. We recommend a meta-analysis to estimate the national prevalence of respiratory allergies.

Breast cancer is the most common carcinoma in women worldwide. The present case-control study was aimed to examine the association of BCL-2 (-938C> A), BAX (-248G > A), and HER2 (I655V i.e. A > G) polymorphisms with breast cancer risk in Indian population. This study enrolled 117 breast cancer cases and 104 controls. BCL-2 (-938C > A), BAX (-248G > A), and HER2 Ile655Val polymorphisms were screened by PCR-RFLP method. There was no significance difference in the allelic and genotype frequency of the BCL-2 (-938C > A) and BAX (-248G > A) polymorphisms between cases and controls. In relation to HER2 Ile655Val polymorphism, the statistical analysis of observed genotypic frequencies showed significant association ( p -0.0059). Compared to Ile/Ile (A/A) genotype, frequency of Ile/Val (A/G) genotype was significantly higher among cases than in control group and observed to increase the breast cancer risk (OR, 2.43; 95%CI, 1.32–4.46; p -0.004). The frequency of Val (G) allele was significantly higher in cases as compared to controls (6.83% vs 2.88%, resp.). Compared to Ile (A) allele, significant increase in the risk of breast cancer was observed with Val (G) allele (OR, 2.21; 95% CI, 1.35–3.63; p -0.0016). We observed significant association between HER2 Ile655Val polymorphism and breast cancer risk under the dominant (OR = 2.52; 95% CI: 1.41–4.51; p -0.001) and codominant (OR, 2.24; 95% CI: 1.23–4.09; p-0.008) model. In our study, BCL-2 (-938C > A) and BAX (-248G > A) polymorphism were not found to be associated with breast cancer risk. This present study for the first time shows significant association of HER2 Ile655Val polymorphism with risk of breast cancer in Indian population. Therefore, we suggest that each population need to evaluate its own genetic profile for breast cancer risk that may be helpful for better understanding the racial and geographic differences reported for breast cancer incidence and mortality.

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (β-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.

A proper execution of basic cellular functions requires well-controlled homeostasis including correct protein folding. Endoplasmic reticulum (ER) implements such functions by protein reshaping and post-translational modifications. Different insults imposed on cells could lead to ER stress-mediated signaling pathways, collectively called the unfolded protein response (UPR). ER stress is also closely linked with oxidative stress, which is a common feature of diseases such as stroke, neurodegeneration, inflammation, metabolic diseases, and cancer. The level of ER stress is higher in cancer cells, indicating that such cells are already struggling to survive. Prolonged ER stress in cancer cells is like an Achilles’ heel, if aggravated by different agents including nanoparticles (NPs) may be exhausted off the pro-survival features and can be easily subjected to proapoptotic mode. Different types of NPs including silver, gold, silica, graphene, etc. have been used to augment the cytotoxicity by promoting ER stress-mediated cell death. The diverse physico-chemical properties of NPs play a great role in their biomedical applications. Some special NPs have been effectively used to address different types of cancers as these particles can be used as both toxicological or therapeutic agents. Several types of NPs, and anticancer drug nano-formulations have been engineered to target tumor cells to enhance their ER stress to promote their death. Therefore, mitigating ER stress in cancer cells in favor of cell death by ER-specific NPs is extremely important in future therapeutics and understanding the underlying mechanism of how cancer cells can respond to NP induced ER stress is a good choice for the development of novel therapeutics. Thus, in depth focus on NP-mediated ER stress will be helpful to boost up developing novel pro-drug candidates for triggering pro-death pathways in different cancers.

In the United States, prevalence of marijuana-use has doubled in the past 2 decades. The aim was to compare the periodontal conditions and whole-salivary IL-17A and IL-23 levels among young adult marijuana-smokers, heavy cigarette-smokers and non-smokers. Self-reported marijuana-smokers, heavy-cigarette-smokers, non-smokers with periodontitis and periodontally-healthy non-smokers were included. Demographic data was recorded and full-mouth plaque index (PI), bleeding on probing (BoP), probing depth (PD) and clinical attachment loss (AL), marginal bone loss (MBL) and missing teeth were recorded. Levels of IL-17A and IL-23 levels were measured in the whole saliva. p &lt, 0.01 was considered statistically significant. Fifteen-marijuana-smokers, 15 heavy-cigarette-smokers, 16 non-smokers-with-periodontitis and 15 periodontally-healthy-non-smokers) were included. The clinicoradiographic parameters were worse among marijuana-smokers (p &lt, 0.01), cigarette-smokers (p &lt, 0.01) and non-smokers-with-periodontitis (p &lt, 0.01) than periodontally-healthy-non-smokers. Marijuana- and cigarette-smokers had Stage-IV/Grade C and non-smokers with periodontitis had Stage-III/Grade-C. Salivary IL-17A and IL-23 levels were higher in marijuana-smokers than cigarette-smokers (p &lt, 0.01). Whole salivary IL-17A and IL-23 levels were higher among cigarette-smokers than non-smokers with periodontitis (p &lt, 0.01) and periodontally-healthy-individuals (p &lt, 0.01). Marijuana- and heavy cigarette-smokers have comparable clinicoradiographic periodontal statuses. This rejects hypothesis-1. However, whole salivary immunoinflammatory response may be moderately worse in marijuana-smokers compared with heavy cigarette-smokers and non-smoker with periodontitis thereby supporting hypothesis-2.

Advanced glycation end products (AGEs) are naturally occurring biomolecules formed by interaction of reducing sugars with biomolecules such as protein and lipids etc., Long term high blood sugar level and glycation accelerate the formation of AGEs. Unchecked continuous formation and accumulation of AGEs are potential risks for pathogenesis of various chronic diseases. Current mode of antidiabetic therapy is based on synthetic drugs that are often linked with severe adverse effects. Polyphenolic compounds derived from plants are supposed to inhibit glycation and formation of AGEs at multiple levels. Some polyphenolic compounds regulate the blood glucose metabolism by amplification of cell insulin resistance and activation of insulin like growth factor binding protein signaling pathway. Their antioxidant nature and metal chelating activity, ability to trap intermediate dicarbonyl compounds could be possible mechanisms against glycation and AGEs formation and hence, against AGEs induced health complications. Although, few species of polyphenolic compounds are being used in in vitro trials and their in vivo study is still in progress, increasing the area of research in this field may produce a fruitful approach in management of overall diabetic complications.

The current study aims to explore the hepatoprotective mechanisms of garlic extract through in vivo and in vitro assays. The in vitro investigation of antioxidant and anti-inflammatory potential showed maximum 67.5% of free radical scavenging and 71.36% albumin denaturation inhibition by 600 &mu, g/mL garlic extract. To explore the hepatoprotective activity by in vivo experiments, the animals were orally intoxicated with 150 &mu, L of CCl4 (1:1 v/v in olive oil) and treated with garlic extract (75 mg/kg b.w.) 3 times/week, for eight successive weeks. The administration of garlic extract significantly ameliorated CCl4 induced increment in amounts of serum Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Aspartate transaminaseas (106.7, 116.3, 136.4 U/L) as compared to disease control which showed increased level (140.5, 156.2, 187.6 U/L). Besides, significant reduction of Superoxide dismutase (SOD), Glutathione peroxidases (GPx), and Glutathione (GSH) (29.3, 48.4, and 25.9 U/mg protein) was noticed in CCl4 induced animals, respectively. Likewise, garlic extract treatment facilitated a significant increment in all tested antioxidant enzymes levels (41.6, 63.3, and 32.5 U/mg protein), respectively. Additionally, Tumor necrosis factor⍺ (TNF-⍺), C-reactive protein (CRP), Interleukin-1&beta, (IL-1&beta, ), Interleukin 6 (IL-6) and ICAM-1 (Intercellular Adhesion Molecule 1) level (63.79, 580.2, 18.3, 63.74 and 148.4 pg/mL) were increased significantly in CCl4-induced group, while garlic extract treatment decreased these pro inflammatory marker levels (40.24, 460.4, 15.4, 45.14, and 125.3 pg/mL). The animals exposed to CCl4 showed various types of alterations like lymphocytes infiltration, edema and congestion, while the animals treated with garlic extract plus CCl4 showed amelioration of the hepatocytes architectures. Thus, our finding advocates that the consumption of garlic can be a potential therapeutic remedy in the inhibition of liver ailments.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are serious clinical complications with a high frequency of morbidity and mortality. The initiation and amplification of inflammation is a well-known aspect in the pathogenesis of ALI and related disorders. Therefore, inhibition of the inflammatory mediators could be an ideal approach to prevent ALI. Epigallocatechin-3-gallate (EGCG), a major constituent of green tea, has been shown to have protective effects on oxidative damage and anti-inflammation. The goal of the present study was to determine whether EGCG improves phenotype and macrophage polarisation in LPS-induced ALI. C57BL/6 mice were given two doses of EGCG (15 mg/kg) intraperitoneally (IP) 1 h before and 3 h after LPS instillation (2 mg/kg). EGCG treatment improved histopathological lesions, Total Leucocyte count (TLC), neutrophils infiltration, wet/dry ratio, total proteins and myeloperoxidase (MPO) activity in LPS-induced lung injury. The results displayed that EGCG reduced LPS-induced ALI as it modulates macrophage polarisation towards M2 status. Furthermore, EGCG also reduced the expression of proinflammatory M1 mediators iNOS TNF-&alpha, IL-1&beta, and IL-6 in the LPS administered lung microenvironment. In addition, it increased the expression of KLF4, Arg1 and ym1, known to augment the M2 phenotype of macrophages. EGCG also alleviated the expression of 8-OHdG, nitrotyrosine, showing its ability to inhibit oxidative damage. TREM1 in the lung tissue and improved lung regenerative capacity by enhancing Ki67, PCNA and Ang-1 protein expression. Together, these results proposed the protective properties of EGCG against LPS-induced ALI in may be attributed to the suppression of M1/M2 macrophages subtype ratio, KLF4 augmentation, lung cell regeneration and regulating oxidative damage in the LPS-induced murine ALI.

AIM: The present study was undertaken to evaluate the possible protective role of thymoquinone on CCl4-induced hepatotoxicity. METHODS: The activities of liver function enzymes and antioxidant enzymes were measured. Haematoxylin-Eosin staining was performed to analyze the live tissue alterations. Additionally, expression pattern of different proteins was evaluated through immunohistochemistry staining. RESULTS: The antioxidants enzymes activities were decreased significantly in the CCl4 induced group whereas recovery/increase of antioxidant enzymes was observed when thymoquinone was given to the mice. Moreover, thymoquinone administration significantly decrease the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum aspartate aminotransferase (AST). Liver tissue alterations were noted in CCl4 treated group whereas treatment with thymoquinone significantly prevented the CCl4-induced histological alteration. The expression of PTEN protein was high in CCl4 plus thymoquinone treated group while the loss of PTEN protein expression was observed in CCl4 treated group. Moreover, high expression of P53 protein was noticed in CCl4 treated the group as compared to CCl4 plus thymoquinone group. Difference in expression pattern of PTEN and p53 protein in CCl4 group and thymoquinone plus CCl4 treated group was statically significant (p < 0.05). Besides, expression of VEGF was high in CCl4 treated group as well as thymoquinone plus CCl4 treated group and difference in expression pattern was statically insignificant (p > 0.05). CONCLUSION: Our results suggest that thymoquinone can protect CCl4 induced liver damage and could be a preventive drug in the development of novel therapeutic agents for liver diseases.

BACKGROUND: Cement contains various types of chemicals in addition to lime and silica, and such chemicals cause different health complications and pathogenesis in addition to respiratory disorders. The most important occupational hazards for cement workers are allergy and complication related to respiratory system.AIM: The current study was performed by analysing the questionnaire distributed among the workers and also by the sputum collected from them to study the general health conditions and other life activities.METHODS: Sputum samples were assayed for cytological analysis by Hematoxylin and Eosin staining.RESULTS: In this study, it was observed that majority of these workers suffered from different types of respiratory complications, such as a cough, asthma and lung infections. In addition to this, few subjects showed allergy and other complication like hypertension, diabetes and backache. Moreover, cytological analysis of the sputum was made, and it was observed that majority of the subjects showed severe inflammation.CONCLUSION: Based on these finding, we concluded that long-term cement dust exposure and inhalation causes respiratory complications due to epithelial tissue damage and that can lead to secondary complications as well.

Acinetobacter baumannii has recently been increasing as an aggressive pathogen in immunocompromised persons. In the present study, we determined the in vitro antibacterial and anti-biofilm activity of thymoquinone (TQ) against A. baumannii. A liposomal formulation of TQ (Lip-TQ) was prepared and its therapeutic potential was investigated in the treatment of A. baumannii infection in immunocompromised mice. Leukopenia was induced in mice by injecting cyclophosphamide (CYP) at a dose of 200 mg/kg and the leukopenic mice were infected with 1 × 106 CFUs of A. baumannii. The effectiveness of free TQ or Lip-TQ against A. baumannii infection was assessed by analyzing the survival rate and bacterial burden. Moreover, the efficacy of Lip-TQ was also studied by examining the systemic inflammatory markers and the histological changes in the lung tissues. The results showed that the mice in the group treated with Lip-TQ at a dose of 10 mg/kg exhibited a 60% survival rate on day 40 post-infection, whereas all the mice treated with free TQ at the same dose died within this duration. Likewise, the lowest bacterial burden was found in the lung tissue of mice treated with Lip-TQ (10 mg/kg). Besides, Lip-TQ treatment remarkably alleviated the infection-associated inflammation, oxidative stress, and histological changes in the lung tissues. Based on the findings of the present study, we recommend considering Lip-TQ as a valuable therapeutic formulation in the treatment of A. baumannii-associated pneumonia in immunocompromised subjects.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.

The emergence of novel coronavirus strain 2019 (COVID-19) linked with pneumonia poses a serious threat to public health worldwide. Firstly, the COVID-19 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of COVID-19 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of COVID-19 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.

Cancer is one of the most leading causes of death worldwide. It is one of the primary global diseases that cause morbidity and mortality in millions of people. It is usually caused by different carcinogenic agents that damage the genetic material and alter the cell signaling pathways. Carcinogens are classified into two groups as genotoxic and non-genotoxic agents. Genotoxic carcinogens are capable of directly altering the genetic material, while the non-genotoxic carcinogens are capable of producing cancer by some secondary mechanisms not related to direct gene damage. There is undoubtedly the greatest need to utilize some novel natural products as anticancer agents, as these are within reach everywhere. Interventions by some natural products aimed at decreasing the levels and conditions of these risk factors can reduce the frequency of cancer incidences. Cancer is conventionally treated by surgery, radiation therapy and chemotherapy, but such treatments may be fast-acting and causes adverse effects on normal tissues. Alternative and innovative methods of cancer treatment with the least side effects and improved efficiency are being encouraged. In this review, we discuss the different risk factors of cancer development, conventional and innovative strategies of its management and provide a brief review of the most recognized natural products used as anticancer agents globally.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. The interaction between various genetic variants and environmental factors triggers T2DM. The aim of this study was to find risk associated with genetic variants rs5210 and rs2237895 of KCNJ11 and KCNQ1 genes, respectively, in the development of T2DM in the Indian population. A total number of 300 cases of T2DM and 100 control samples were studied to find the polymorphism in KCNJ11 and KCNQ1 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different compared to the control population. KCNJ11 rs5210 and KCNQ1 rs2237895 variants were found to be significantly associated with risk of T2DM in dominant (KCNJ11: OR, 2.07; 95% CI, 1.30–3.27; p−0.001; KCNQ1: OR, 2.33; 95% CI, 1.46–3.70; p−0.0003) and codominant models (KCNJ11: OR, 1.76; 95% CI, 1.09–2.84; p−0.020; KCNQ1: OR, 1.85; 95% CI, 1.16–2.95; p−0.009). We also compared clinicopathological characteristics between cases and control and observed a significant difference in all the parameters except HDL, gender, and family history. In this study, clinicopathological data with a carrier of a variant allele of both KCNJ11 and KCNQ1 genes were also analysed, and a significant association was found between the carrier of a variant allele with gender and PPG in KCNJ11 and with triglyceride in KCNQ1. We confirm the significant association of KCNJ11 (rs5210) and KCNQ1 (rs2237895) gene polymorphism with T2DM, indicating the role of these variants in developing risk for T2DM in Indian population.

Background:A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant–associated ALCL and, if so, to compare the bacterial microbiome to

BACKGROUND: Tuberculosis is a chronic inflammatory disease with lymphadenopathy being the most common extra-pulmonary manifestation. The conventional Ziehl–Neelsen method plays an essential role in the diagnosis of tuberculosis; however, it has a low sensitivity in detecting acid-fast bacilli. AIM: The present study emphasises the role of the microwave-heated method (modified Ziehl–Neelsen) over conventional Ziehl-Neelsen stain and to set at the best condition for irradiation. MATERIAL AND METHODS: The study included 90 patients with clinically suspected tuberculous lymphadenopathy who were referred to the Department of Pathology at Omdurman Military Hospital, Sudan. Demographic data such as age, sex, and site of swelling were documented for each patient. Specimens were stained with conventional Ziehl-Neelsen, fluoresce and the modified methods. RESULTS: Patient’s age ranged from 20 to 70 year. Of the total 90 cases with clinically suspected tuberculous lymphadenopathy, 18 cases were positive for AFB in conventional Ziehl-Neelsen method giving a sensitivity of 13.3%, while in microwave-heated method 82 cases of TB were detected positive for AFB yielded sensitivity and specificity of 97.6% and 85.7%, respectively, and positive and negative predictive values of 98.8% and 75.0% respectively compared to fluorescence methods. CONCLUSION: In the present study, the microwave-heated Ziehl-Neelsen method, was found to have sensitivity and specificity of 97.6% and 85.7%, respectively which matches the fluorescence technique. It has specificity in detecting lymph node tuberculosis that makes it superior over all other modified methods. However, the availability and cost-effectiveness might limit the use of fluorescence in routine practice. Furthermore, the study set the best staining temperature is provided at power 1 level (60 w) for 1.5 minutes.

Protein glycation and oxidative stress lead to severe health complications in various diseases including diabetes mellitus. The intake of flavonoid-rich foods has been confirmed previously to have a positive effect on human health. Ginger is an important source of flavonoids and is one of the most widely used traditional medicines in many Asian countries. The aim of this study was to verify the therapeutic potential of methanolic extract from ginger against glycation and other oxidative stress-induced complications using in vitro study. In this study, quantitative estimations of antioxidant components such as total phenolic and flavonoids were determined by UV&ndash, visible spectrophotometry. The anti-inflammatory action of the ginger extract was checked by determining its protective action against the denaturation of proteins, anti-proteinase activity and its membrane stabilization effect. The anti-inflammatory action of ginger extract was found to be comparable with reference standard drugs. The antiglycating effect of ginger extract was investigated by placing bovine serum albumin (BSA) with glucose in the presence and absence of ginger extract for two weeks at 37 &deg, C. The incubated samples were analyzed for the number of glycation products, secondary structural changes, aggregation and advanced glycation end products (AGEs) formation by checking browning intensity, determination of aggregation index and Congo red assays. Our findings demonstrated that ginger extract (600 &micro, g/mL) significantly reduced the browning, secondary structural changes, aggregation and AGEs formation. Thus, it can be concluded from these results that ginger extract is a wealthy source of antioxidants and can be used to prevent the glycation and oxidative stress-induced damage of biomolecules in various health complications including inflammation.

Numerous studies have been performed in understanding the development of cancer. Though, the mechanism of action of genes in the development of cancer remains to be explained. The current mode of treatment of cancer shows adverse effects on normal cells and also alter the cell signalling pathways. However, ginger and its active compound have fascinated research based on animal model and laboratories during the past decade due to its potentiality in killing cancer cells. Ginger is a mixture of various compounds including gingerol, paradol, zingiberene and shogaol and such compounds are the main players in diseases management. Most of the health-promoting effects of ginger and its active compound can be attributed due to its antioxidant and anti-tumour activity. Besides, the active compound of ginger has proven its role in cancer management through its modulatory effect on tumour suppressor genes, cell cycle, apoptosis, transcription factors, angiogenesis and growth factor. In this review, the role of ginger and its active compound in the inhibition of cancer growth through modulating cell signalling pathways will be reviewed and discussed.

Background: Squamous cell carcinoma (SCC) of the uterine cervix is a leading cause of morbidity and mortality among women. The alterations of Phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl2) and p53 expression seem to be significant in the development of various types of cancers. The altered expressions of PTEN, Bcl2 and p53 and their involvement in cancer of the uterine cervix are not well recognized. Aim: This study aimed at examining the expression patterns of PTEN, Bcl2 and p53 proteins and comparing them with the grade and stage of cervical cancer. Materials and Methods: Tissue blocks of SCC and ten cases of inflammatory lesions of the uterine cervix were examined immunohistochemically for the expression of PTEN, Bcl2 and p53 proteins. Results: Loss of PTEN expression was identified in 45.33% of cervical SCC and no expression was found in inflammatory lesions (p &le, 0.05). PTEN expression was significantly associated with the clinical stage of SCC (61.36% and 45.16% in stages I&ndash, II and III&ndash, IV, respectively) (p &lt, 0.05), but not with the degree of differentiation of the SCC. The expression of Bcl2 was significantly high (60%) in cancer cases than in control cases (p &lt, 0.05). Bcl2 did not show any significant association with the histologic type and clinical stage of the SCC of the uterine cervix. The expression of p53 protein was significantly high (57.33%)) in cancer tissue, and no expression was noted in control cases (p &lt, 0.05). Moreover, the expression pattern of p53 protein in cervical cancer tissue samples was not linked with the patient age, grade and stage of the cervical SCC (p &gt, 0.05). Conclusion: The reduced expression of PETN and overexpressions of Bcl2 and p53 might play an indispensable role in carcinogenesis of cervical SCC. Moreover, a relationship was detected between PTEN expression and clinical stage of the cervical SCC.