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Aakash Pandita,1 Deepak Sharma,2 Dharti Pandita,3 Smita Pawar,4 Mir Tariq,5 Avinash Kaul6 1Department of Pediatrics, SMGS Hospital Jammu, Jammu and Kashmir, India; 2Department of Pediatrics, Pt Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India; 3Department of Microbiology Jammu University, Jammu, Jammu and Kashmir, India; 4Department of OBG Fernandez Hospital, Hyderabad,Telangana, India; 5Department of Orthopedics, Kokilaben Dhirubhai Ambani Hospital, Mumbai, India; 6Department of Surgery, Acharya Shri Chander College of Medical Sciences and Hospital, Jammu, Jammu and Kashmir, India Abstract: Obesity and its associated comorbidities have emerged as a major health problem garnering interests from both public health agencies and mainstream media consumers. With increasing awareness on its impact on health, finances, and community at large, it has come to the forefront for scientific research and development of health plans. The need for better strategies and novel interventions to manage obesity is now being recognized by the entire health care system. Obesity and overweight is now the fifth leading global risk factor for mortality. Strategic investment is thus urgently needed to implement population-based childhood obesity prevention programmes which are effective and also culturally appropriate. Population-based prevention is crucial to stem this rising tide of childhood obesity which is fast reaching epidemic proportions. Obesity has its onset very early in life; therefore, children constitute a major group of this disease. It is thus imperative to lay utmost importance on prevention of obesity in children and herald its progress, if present already. Furthermore, treatment is still in preliminary stage, so early prevention holds better than treatment at later stages. This article is an attempt to lay emphasis on childhood obesity as a problem that needs to be recognized early and measures for its prevention. Keywords: overweight, obesity, prevention, assessment, body mass index, nutrition assessment, treatment

Breast cancer ranks as the most widespread malignant condition in women, emerging as a primary contributor to mortality. The primary challenges in cancer treatments involve undesirable side effects. Therefore, exploring natural compounds as additional therapy could provide valuable insights. Isoliquiritigenin (ILN), an isoflavonoid featuring a chalcone moiety primarily sourced from Glycyrrhiza species, has garnered increasing interest in breast cancer research. This review aims to provide a comprehensive understanding of ILN's mechanisms of action in breast cancer, drawing from a range of in vitro and in vivo studies. ILN primarily acts by inhibiting angiogenesis, aromatase, inflammation, and cell proliferation, and preventing invasion and metastasis. Mechanistically, it downregulates miR-374a, phosphoinositide-3-kinase-protein kinase B/Akt, maternal embryonic leucine zipper kinase, vascular endothelial growth factor, and estrogen receptor protein levels, and causes enhancement of Wnt inhibitory factor-1, and Unc-51-like kinase 1 expression to treat breast cancer. ILN emerges as a promising natural option, offering therapeutic advantages with minimal side effects. However, it is important to note that current research on ILN is primarily limited to preclinical models, underscoring the need for further investigation to validate its potential efficacy., Competing Interests: Declarations. Ethical approval: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Large language models (LLMs) continue to exhibit noteworthy capabilities across a spectrum of areas, including emerging proficiencies across the health care continuum. Successful LLM implementation and adoption depend on digital readiness, modern infrastructure, a trained workforce, privacy, and an ethical regulatory landscape. These factors can vary significantly across health care ecosystems, dictating the choice of a particular LLM implementation pathway. This perspective discusses 3 LLM implementation pathways-training from scratch pathway (TSP), fine-tuned pathway (FTP), and out-of-the-box pathway (OBP)-as potential onboarding points for health systems while facilitating equitable adoption. The choice of a particular pathway is governed by needs as well as affordability. Therefore, the risks, benefits, and economics of these pathways across 4 major cloud service providers (Amazon, Microsoft, Google, and Oracle) are presented. While cost comparisons, such as on-demand and spot pricing across the cloud service providers for the 3 pathways, are presented for completeness, the usefulness of managed services and cloud enterprise tools is elucidated. Managed services can complement the traditional workforce and expertise, while enterprise tools, such as federated learning, can overcome sample size challenges when implementing LLMs using health care data. Of the 3 pathways, TSP is expected to be the most resource-intensive regarding infrastructure and workforce while providing maximum customization, enhanced transparency, and performance. Because TSP trains the LLM using enterprise health care data, it is expected to harness the digital signatures of the population served by the health care system with the potential to impact outcomes. The use of pretrained models in FTP is a limitation. It may impact its performance because the training data used in the pretrained model may have hidden bias and may not necessarily be health care-related. However, FTP provides a balance between customization, cost, and performance. While OBP can be rapidly deployed, it provides minimal customization and transparency without guaranteeing long-term availability. OBP may also present challenges in interfacing seamlessly with downstream applications in health care settings with variations in pricing and use over time. Lack of customization in OBP can significantly limit its ability to impact outcomes. Finally, potential applications of LLMs in health care, including conversational artificial intelligence, chatbots, summarization, and machine translation, are highlighted. While the 3 implementation pathways discussed in this perspective have the potential to facilitate equitable adoption and democratization of LLMs, transitions between them may be necessary as the needs of health systems evolve. Understanding the economics and trade-offs of these onboarding pathways can guide their strategic adoption and demonstrate value while impacting health care outcomes favorably., (©Radha Nagarajan, Midori Kondo, Franz Salas, Emre Sezgin, Yuan Yao, Vanessa Klotzman, Sandip A Godambe, Naqi Khan, Alfonso Limon, Graham Stephenson, Sharief Taraman, Nephi Walton, Louis Ehwerhemuepha, Jay Pandit, Deepti Pandita, Michael Weiss, Charles Golden, Adam Gold, John Henderson, Angela Shippy, Leo Anthony Celi, William R Hogan, Eric K Oermann, Terence Sanger, Steven Martel. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.11.2024.)

Primary care informatics (PCI) professionals address workflow and technology solutions in a wide spectrum of health, ranging from optimizing the experience of the individual patient in the clinic room to supporting the health of populations and augmenting the work of frontline primary care clinical teams. PCI overlaps uniquely with 2 disciplines with an impact on societal health-primary care and health informatics. Primary care is a gateway to health care access and aims to synthesize and coordinate numerous, complex elements of patients' health and medical care in a holistic manner. However, over the past 25 years, primary care has become a specialty in crisis: in a post-COVID-19 world, workforce shortages, clinician burnout, and continuing challenges in health care access all contribute to difficulties in sustaining primary care. Informatics professionals are poised to change this trajectory. In this viewpoint, we aim to inform readers of the discipline of PCI and its importance in the design, support, and maintenance of essential primary care services. Although this work focuses on primary care in the United States, which includes general internal medicine, family medicine, and pediatrics (and depending on definition, includes specialties such as obstetrics and gynecology), many of the principles outlined can also be applied to comparable health care services and settings in other countries. We highlight (1) common global challenges in primary care, (2) recent trends in the evolution of PCI (personalized medicine, population health, social drivers of health, and team-based care), and (3) opportunities to move forward PCI with current and emerging technologies using the 4Cs of primary care framework. In summary, PCI offers important contributions to health care and the informatics field, and there are many opportunities for informatics professionals to enhance the primary care experience for patients, families, and their care teams., (©Jacqueline Guan-Ting You, Tiffany I Leung, Deepti Pandita, Matthew Sakumoto. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.10.2024.)

Competing Interests: Disclosures: All relevant financial relationships have been mitigated. Disclosure forms are available with this article online.

Internal medicine physicians are increasingly interacting with systems that implement artificial intelligence (AI) and machine learning (ML) technologies. Some physicians and health care systems are even developing their own AI models, both within and outside of electronic health record (EHR) systems. These technologies have various applications throughout the provision of health care, such as clinical documentation, diagnostic image processing, and clinical decision support. With the growing availability of vast amounts of patient data and unprecedented levels of clinician burnout, the proliferation of these technologies is cautiously welcomed by some physicians. Others think it presents challenges to the patient-physician relationship and the professional integrity of physicians. These dispositions are understandable, given the "black box" nature of some AI models, for which specifications and development methods can be closely guarded or proprietary, along with the relative lagging or absence of appropriate regulatory scrutiny and validation. This American College of Physicians (ACP) position paper describes the College's foundational positions and recommendations regarding the use of AI- and ML-enabled tools and systems in the provision of health care. Many of the College's positions and recommendations, such as those related to patient-centeredness, privacy, and transparency, are founded on principles in the ACP Ethics Manual. They are also derived from considerations for the clinical safety and effectiveness of the tools as well as their potential consequences regarding health disparities. The College calls for more research on the clinical and ethical implications of these technologies and their effects on patient health and well-being., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0146.

Various substances possessing radiation scavenging properties, known as radioprotectors, play a crucial role in shielding organisms from the harmful effects of ionizing radiation (IR) by preventing cellular damage caused by free radicals. Initially, synthetic radioprotectors were developed using thiol synthetic compounds. However, among these, only amifostine (WR-2721) underwent clinical testing as a radioprotector. Various composites with different chemical structures other than thiol compounds were also investigated. However, synthetic radioprotectors are known to be associated with severe side effects, which lead to an inclination towards natural substances. Plants and natural products have emerged as promising sources of radioprotectors, renowned for their non-toxic nature across a broad range of doses and their cost-effectiveness. Radioprotectors are employed in diverse pharmaceutical approaches to mitigate the toxicities induced by radiation. The present review encompasses a detailed account of various synthetic and naturally occurring compounds possessing radioprotective properties, and different investigations related to their radioprotective action, ranging from free radicals scavenging to gene therapy, have also been precisely covered. Numerous radioprotectors have different mechanisms of action, and have proven benefits of naturally occurring compounds over chemically synthesized ones., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Temozolomide (TMZ) is an alkylating agent approved for the management of glioblastoma. The TMZ is not known for progressive multifocal leukoencephalopathy (PML). The main objective of the current study is to find out the association of TMZ with PML using disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data integrated with network pharmacological approaches., Research Design and Methods: OpenVigil tool was used to query the FAERS database. The disproportionality measures were calculated. The network has been constructed using Cytoscape. Finally, the possible binding interactions were studied using Glide, Schrödinger Inc., Results: A total number of 3502 cases of PML were reported in the FAERS database. Out of these, 10 cases were found with TMZ. The subgroup analysis results have shown a greater number of cases in females. The network has indicated the involvement of human mitogen-activated protein kinase, 3-phosphoinositide-dependent protein kinase 1 protein, human mTOR complex protein, phosphatidylinositol 4,5-bisphosphate 3-kinase protein, and glycogen synthase kinase-3 beta protein. The docking results have indicated good interactions of TMZ with active site of glycogen synthase kinase-3 beta and mitogen-activated protein kinase 1 as compared to other identified targets., Conclusion: The PML is identified as novel signal with temozolomide.

Introduction: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment., Content: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack., Summary and Outlook: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Calcitonin gene-related peptide (CGRP) antagonists are recently approved for the treatment of migraine., Aim: The main aim of the current study was to find out the association of CGRP antagonists with RP using data mining algorithms integrated with network pharmacological approaches., Research Design and Methods: The individual case safety reports were extracted using OpenVigil2.1-MedDRA-V17 (2004Q1-2022Q3), the United States Adverse Event Reporting System (US FAERS). The data mining algorithms i.e. reporting odds ratio (ROR) with 95% confidence and proportionality reporting ratio (PRR) with associated chi-square value were calculated along with a minimum of three ICSRs to identify the signal. Further, the network was constructed using Cytoscape 3.7.2. Finally, molecular docking was performed using Glide, Schrodinger Inc., Results: The PRR ≥2 with a linked chi-square value ≥4, add up of co-occurrence ≥3, and a lower limit of 95% confidence interval of ROR exceeding 2 indicates a positive signal of RP. Further, the network pharmacological and molecular docking results have shown the involvement of insulin-like growth factor 1-receptor (IGF1R) pathways., Conclusion: The RP is recognized as a novel signal with all CGRP antagonists.

Acute myeloid leukemia (AML), a heterogeneous hematopoietic cancer prevalent in adults, has been a leading cause of leukemia-associated deaths for decades. Despite advancements in understanding its pathology and pharmacological targets, therapeutic strategies have seen minimal change. The standard treatment, combining cytarabine and anthracycline, has persisted, accompanied by challenges such as pharmacokinetic issues and non-specific drug delivery, leading to severe side effects. Nanotechnology offers a promising solution through combination drug delivery. FDA-approved CPX351 (VYXEOS™) a liposomal formulation delivering doxorubicin and cytarabine, exemplifies enhanced therapeutic efficacy. Ongoing research explores various nanocarriers for delivering multiple bioactives, addressing drug targeting, pharmacokinetics and chemoresistance. This review highlights nanotechnology-based combination therapies for the effective management of AML, presenting a potential breakthrough in leukemia.

Objectives: The number of surgeries performed in the United States has increased over the past two decades, with a shift to the ambulatory setting. Perioperative complications and mortality pose significant health care burdens. Inadequate preoperative assessment and documentation contribute to communication failure and poor patient outcomes. The aim of this quality improvement project was to design and implement a preoperative evaluation documentation template that not only improved communication during the perioperative pathway but also enhanced the overall user experience., Methods: We implemented a revamped evidence-based documentation template in the electronic medical records of a health care organization across three internal medicine clinics on the downtown campus and seven satellite family medicine clinics. A pre- and postintervention design was used to assess the template utilization rate and clinician satisfaction., Results: The preoperative template utilization rate increased from 51.2% at baseline to 66.5% after the revamped template "went live" ( p  < 0.001). Clinician satisfaction with the preoperative documentation template also significantly increased (30.6 vs. 80.0%, p  < 0.001)., Conclusion: Adopting a user-friendly, evidence-based documentation template can enhance the standardization of preoperative evaluation documentation and reduce the documentation burden., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures., Objectives: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses., Methods: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, fellows, administrative support, funding sources, and expenses. We surveyed program directors of programs accredited by the Accreditation Council for Graduate Medical Education between 2014 and 2021., Results: We invited 54 program directors, of which 41 (76%) completed the survey. The average administrative support received was $27,732/year. Most programs (85.4%) were accredited to have two or more fellows per year. Programs were administratively housed under six departments: Internal Medicine (17; 41.5%), Pediatrics (7; 17.1%), Pathology (6; 14.6%), Family Medicine (6; 14.6%), Emergency Medicine (4; 9.8%), and Anesthesiology (1; 2.4%). Funding sources for CI fellowship program directors included: hospital or health systems (28.3%), clinical departments (28.3%), graduate medical education office (13.2%), biomedical informatics department (9.4%), hospital information technology (9.4%), research and grants (7.5%), and other sources (3.8%) that included philanthropy and external entities., Conclusion: CI fellowships have been established in leading academic and community health care systems across the country. Due to their unique training requirements, these programs require significant resources for education, administration, and recruitment. There continues to be considerable heterogeneity in funding models between programs. Our survey findings reinforce the need for reformed federal funding models for informatics practice and training., Competing Interests: None declared., (Thieme. All rights reserved.)

Leiomyosarcoma (LMS) is a subtype of sarcoma derived from smooth muscle cells. Unfortunately, this malignancy has a high rate of metastatic disease. Palliative systemic therapy has historically relied on cytotoxic agents such as doxorubicin, which have low rates of response. Immunotherapy has not been shown to be effective for most patients with sarcoma, including those with LMS. However, this has not been well described for patients with LMS and high tumour mutational burden (TMB). Herein, we report the case of a woman in her late 50s with metastatic high TMB (>10) leiomyosarcoma treated with pembrolizumab., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

A three-dimensional (3D) printing is a robotically controlled state-of-the-art technology that is promising for all branches of engineering with a meritorious emphasis to biomedical engineering. The purpose of 3D printing (3DP) is to create exact superstructures without any framework in a brief period with high reproducibility to create intricate and complex patient-tailored structures for organ regeneration, drug delivery, imaging processes, designing personalized dose-specific tablets, developing 3D models of organs to plan surgery and to understand the pathology of disease, manufacturing cost-effective surgical tools, and fabricating implants and organ substitute devices for prolonging the lives of patients, etc. The formulation of bioinks and programmed G codes help to obtain precise 3D structures, which determines the stability and functioning of the 3D-printed structures. Three-dimensional printing for medical applications is ambitious and challenging but made possible with the culmination of research expertise from various fields. Exploring and expanding 3DP for biomedical and clinical applications can be life-saving solutions. The 3D printers are cost-effective and eco-friendly, as they do not release any toxic pollutants or waste materials that pollute the environment. The sampling requirements and processing parameters are amenable, which further eases the production. This review highlights the role of 3D printers in the health care sector, focusing on their roles in tablet development, imaging techniques, disease model development, and tissue regeneration., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Purpose: Intratumoral hypoxia in non-Hodgkin's Lymphoma (NHL) may interfere with chimeric antigen receptor T-cell (CAR-T) function. We conducted a single-center pilot study (clinicaltrials.gov ID NCT04409314) of [ 18 F]fluoroazomycin arabinoside, a hypoxia-specific radiotracer abbreviated as [ 18 F]FAZA, to assess the feasibility of this positron emission tomography (PET) imaging modality in this population., Methods: Patients with relapsed NHL being evaluated for CAR-T therapy received a one-time [ 18 F]FAZA PET scan before pre-CAR-T lymphodepletion. A tumor to mediastinum (T/M) ratio of 1.2 or higher with regard to [ 18 F]FAZA uptake was defined as positive for intratumoral hypoxia. We planned to enroll 30 patients with an interim futility analysis after 16 scans., Results: Of 16 scanned patients, 3 had no evidence of disease by standard [ 18 F]fluorodeoxyglucose PET imaging before CAR-T therapy. Six patients (38%) had any [ 18 F]FAZA uptake above background. Using a T/M cutoff of 1.20, only one patient (a 68-year-old male with relapsed diffuse large B-cell lymphoma) demonstrated intratumoral hypoxia in an extranodal chest wall lesion (T/M 1.35). Interestingly, of all 16 scanned patients, he was the only patient with progressive disease within 1 month of CAR-T therapy. However, because of our low overall proportion of positive scans, our study was stopped for futility., Conclusions: Our pilot study identified low-level [ 18 F]FAZA uptake in a small number of patients with NHL receiving CAR-T therapy. The only patient who met our pre-specified threshold for intratumoral hypoxia was also the only patient with early CAR-T failure. Future plans include exploration of [ 18 F]FAZA in a more selected patient population., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

New targeted therapy for triple negative breast cancer (TNBC) is an urgent need, as advanced disease responds poorly to conventional chemotherapy. Genomic and proteomic studies are currently investigating new genes and proteins as promising therapeutic targets. One of such therapeutic targets is a cell cycle regulatory kinase; Maternal Embryonic Leucine Zipper Kinase (MELK), overexpressed in TNBC and correlated with cancer development. We performed molecular docking for virtual screening of chemical libraries (phytochemicals/synthetic drugs) against MELK protein structure and identified 8 phytoconstituents (isoxanthorin, emodin, gamma-coniceine, quercetin, tenuazonic acid, isoliquiritigenin, kaempferol, and Nobiletin) and 8 synthetic drugs (tetrahydrofolic acid, alfuzosin, lansoprazole, ketorolac, ketoprofen, variolin B, orantinib, and firestein) as potential hits interacting with the active site residues of MELK based on bound poses, hydrogen bond, hydrophobic interactions and MM/GBSA binding free energies. ADME and drug-likeness prediction further identified few hits with high drug-likeness properties and were further tested for anti-tumorigenic potential. Two phytochemicals isoliquiritigenin and emodin demonstrated growth inhibitory effects on TNBC MDA-MB-231 cells while much lower effect was observed on non-tumorigenic MCF-10A mammary epithelial cells. Treatment with both molecules downregulated MELK expression, induced cell cycle arrest, accumulated DNA damage and enhanced apoptosis. The study identified isoliquiritigenin and emodin as potential MELK inhibitors and provides a basis for subsequent experimental validation and drug development against cancer., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Rice is a key food grain contributor to the global food grain basket and is considered the main food crop in India with a large number of varieties released every year. SSR markers have proven to be an excellent tool for studying genetic diversity. As a result, the present study was done to characterize and assess genetic diversity as well as population structural aspects., Methods and Results: Fifty genotypes of rice were characterized using 40 SSR markers to assess the genetic diversity and genetic relationship. A total of 114 alleles were amplified with an average of 2.85 alleles per locus. The Polymorphism Information Content (PIC) values varied from 0.30 (RM162) to 0.58 (RM413) with an average of 0.44. Gene diversity was in the range of 0.35 (RM162) to 0.66 (RM413), with an average value of 0.52, while heterozygosity ranged from 0.18 (RM27) to 0.74 (RM55), with an average of 0.39. The population structure revealed a narrow genetic base with only three major subpopulations. Analysis of molecular variance revealed that 74% of the variation was attributed within individuals, 23% was among individuals, and 3% was among populations. Pairwise Fst value of population A & B is 0.024, population B & C is 0.120 and population A & C is 0.115. Dendrogram grouped the genotypes into three clusters with wide variation among the accessions., Conclusion: Genotyping combined with phylogeny and population structure analysis proved to be a powerful method for characterizing germplasm in this study. There is significant gene flow within populations, as well as the presence of different combinations of alleles, and that allelic exchange rates within the populations are higher than among the populations. Assessing the genetic diversity among individual genotypes within populations is quite useful in selecting candidate parents for future breeding programs to improve the target traits in rice for the Himalayan region., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Cell division cycle 20 (CDC20), a critical partner of anaphase promoting complex (APC/C), is indispensably required for metaphase-to-anaphase transition. CDC20 overexpression in TNBC breast cancer patients has been found to be correlated with poor prognosis, hence, we aimed to target CDC20 for TNBC therapeutics. In silico molecular docking of large-scale chemical libraries (phytochemicals/synthetic drugs) against CDC20 protein structure identified five synthetic drugs and four phytochemicals as potential hits interacting with CDC20 active site. The molecular selection was done based on docking scores, binding interactions, binding energies and MM/GBSA scores. Further, we analysed ADME profiles for all the hits and identified lidocaine, an aminoamide anaesthetic group of synthetic drug, with high drug-likeness properties. We explored the anti-tumorigenic effects of lidocaine on MDA-MB-231 TNBC breast cancer cells, which resulted in increased growth inhibition in dose-dependent manner. The molecular mechanism behind the cell viability defect mediated by lidocaine was found to be induction of G2/M cell cycle arrest and cellular apoptosis. Notably, lidocaine treatment of TNBC cells also resulted in downregulation of CDC20 gene expression. Thus, this study identifies lidocaine as a potential anti-neoplastic agent for TNBC cells emphasizing CDC20 as a suitable therapeutic target for breast cancer., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03554-7., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Herpes simplex virus (HSV) infection, the most prevalent viral infection that typically lasts for a lifetime, is associated with frequent outbreaks of oral and genital lesions. Oral herpes infection is mainly associated with HSV-1 through oral contact, while genital herpes originates due to HSV-2 and is categorized under sexually transmitted diseases. Immunocompromised patients and children are more prone to HSV infection. Over the years, various attempts have been made to find potential targets for the prevention of HSV infection. Despite the global distress caused by HSV infections, there are no licensed prophylactic and therapeutic vaccines available on the market against HSV. Nevertheless, there are numerous promising candidates in the pre-clinical and clinical stages of study. The present review gives an overview of two herpes viruses, their history, and life cycle, and different treatments adopted presently against HSV infections and their associated limitations. Majorly, the review covers the recent investigations being carried out globally regarding various vaccine strategies against oral and genital herpes virus infections, together with the recent and advanced nanotechnological approaches for vaccine development. Consequently, it gives an insight to researchers as well as people from the health sector about the challenges and upcoming solutions associated with treatment and vaccine development against HSV infections.

Competing Interests: J.A. is a member of the Platform for AI Ethics, Netherlands Institute for Standardization (NEN), member of the NEN 7542 workgroup on standardization of medication process data and contract reviewer for the European Commission. S.A.-A. has received consulting fees from AstraZeneca, Agilent Biotechnologies, and Diazyme. A.D.B. has received grants or contracts from NIH and NSF, payment or honoraria from Adelphi University, and travel support from Microsoft. A.J.B. is a cofounder of and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, and Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non–health-related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical or disease specific foundations and associations, and health systems. A.J.B. receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. A.J.B.'s research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor's Office of Planning and Research, California Institute for Regenerative Medicine, L'Oreal, and Progenity. A.B.C. has received consulting fees from Invitae Corporation. J.K.C. has received grants or contracts from the Office of Rural Health and Office of Healthcare and Equity, VHA. P.L.E. has received grants or contracts from NLM, NIAAA, and NCATS. Oluseyi Fayanju has received grants or contracts from GetSmarter. L.J.F. serves as a consultant to the American Psychiatric Association, has received travel support in relation to that role, and has also received grant support from NIMH. B.R.J. has received stock or stock options from Consent Vault, LLC. V.N.-J. occupies leadership or fiduciary roles with the Academy of Breastfeeding Medicine and West Central Illinois Breastfeeding Task Force. Ross Koppel has received consulting fees from advisors who contemplate investment in EHR companies, payment or honoraria from University at Buffalo, payment for expert testimony from the U.S. Department of Justice, stock or stock options from TrekIT, and occupies editor roles with the Journal of Applied Clinical Informatics and the International Journal of Medical Informatics. B.K. has received payment or honoraria from the Fall DeVos Medical Ethics Colloquy, and travel support to attend CSHI and AMIA conferences. C.U.L. has received royalties or licenses from Springer, has participated in a Data Safety monitoring board conducted by Lipika Samal at Harvard, and has received stock or stock options from Markel and Celanese. Z.C.L. has received consulting fees from Atrius Health, travel support from the University of Washington, Atrius Health, and Jackson Health System. R.J.M. has supported the present manuscript as a Texas Health Resources Clinical Scholar, has received grants or contracts from the Centers for Disease Control and Prevention, Sergey Brin Family Foundation, and Verily Life Sciences, payment or honoraria from Clinical Infectious Diseases, and occupies a leadership role with the Infectious Diseases Society of America. E.R.M. has received grants or contracts from the National Institute on Drug Abuse, the American Medical Association, and the Agency for Healthcare Research and Quality. A.B.N. has received grants or contracts from Royal Phillips and Eli Lilly, consulting fees from Intuity Medical, Roche, Eli Lilly, Sanofi, Greenberg Traurig, and Medtronic, payment or honoraria from The Doctors Company and TCOYD, and payment for expert testimony from AMFS. L.L.N. has received grants or contracts from GetPreCiSe, Florida State University, AHRQ, Baptist Memorial Healthcare Corporation, IBM Watson Health, and NIH/NIDDK. Deepti Pandita has received travel support from AMIA, has a patent pending with WellPulse app, and is a board member of AMIA. Raghuveer Puttagunta is a board member of Pennsylvania Medical Society. Angela Ryan is a member of AMIA and vice chair of the Australasian Institute of Digital Health. K.M.R. occupies a leadership role with the Society of Hospital Medicine Public Policy Committee. Neda Ratanawongsa occupies a leadership role with the San Francisco General Foundation. K.A.S. has received grants from Meds360 and Anonymous Foundation, honoraria from Stanford, travel support from the Society of Family Planning, and is a volunteer board member of the Society of Family Planning. Vignesh Subbian has received a grant from the National Science Foundation and occupies a leadership role with the AMIA ELSI Working Group. Ida Sim is a scientific advisor with Myovant Sciences. A.S. has received grants from NCATS Chicago Institute for Translational Medicine and PCORI Capricorn CRN, occupies leadership roles with the American Medical Informatics Association and IEEE Standards Association, and owns stock from Pfizer, Moderna, and J.B.S. holds leadership roles in AMIA and in the American College of Medical Informatics (ACMI), has received research funding from NIH and the Greenwall Foundation, and honoraria or consulting fees from the University of Kentucky, the University of Wisconsin, and the Icahn Mount Sinai School of Medicine. Peter Winkelstein has received a grant or contract from CTSA. J.X. has participated on a Data Safety Monitoring Board or Advisory Board with AfaSci, Inc. and Develo. C.Z. has received grants or contracts from CVS Foundation and Ariadne Labs, royalties, or licenses from UpToDate, consulting fees from Blue Cross Blue Shield of Massachusetts, and occupies leadership or fiduciary roles with the American Heart Association, Society for Maternal Fetal Medicine, and ACOG.

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted., Competing Interests: Conflict of interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Breast cancer is one of the most common malignancies and a leading cause of cancer-related mortality among women worldwide. The elements of group XIV in the periodic table exhibit a wide range of chemical manners. Recently, there have been remarkable developments in the field of nanobiomedical research, especially in the application of engineered nanomaterials in biomedical applications. In this review, we concentrate on the recent investigations on the antiproliferative effects of nanomaterials of the elements of group XIV in the periodic table on breast cancer cells. In this review, the data available on nanomaterials of group XIV for breast cancer treatment has been documented, providing a useful insight into tumor biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Objective: We sought to ascertain perceived factors affecting women's career development efforts in the American Medical Informatics Association (AMIA) and to provide recommendations for improvements., Materials and Methods: Data were collected using a 27-item survey administered via the AMIA newsletter and other social channels. Survey questions comprised 3 demographics, 15 Likert-scale, and 9 open-ended items. Likert-scale responses were summarized across respondent ages, career stages, and career domains, and open-ended responses were thematically analyzed., Results: We received survey responses from 109 AMIA women members. Our findings demonstrate that AMIA had made strides in promoting career development, and the most effective AMIA efforts included social events (83%), panel discussions (80%), and scientific sessions (79%). However, despite these efforts, women members perceived that gender-specific challenges persisted within AMIA, and recognized the need for increased networking opportunities (96%), raising awareness of gender-specific challenges (95%), and encouraging gender proportional representation in leadership (92%)., Discussion: International and national biomedical informatics professional communities have put forth efforts to address gender-specific issues in career development. Yet, our study identified that some of these, including the deep-rooted gender power hierarchy and bias, are still perceived as profound in AMIA., Conclusion: Even though existing career development efforts for women are highly effective, important perceived gender-specific career development issues require further attention and investigation to improve existing AMIA activities., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Powdery mildew is an omnipresent disease that reduces the yield and quality of pea crops ( Pisum sativum L.). To examine the powdery mildew pathogen's morphological, molecular, and genetic diversity, we collected samples of powdery mildew-affected pea crops from ten distinct locations in the Nilgiris district of Tamil Nadu, India. The pathogen Erysiphe pisi was identified morphologically based on anamorphic characters. Molecular identification of E. pisi isolates was befitted by targeting the internal transcribed spacer (ITS) region of rDNA and specific primers of powdery mildew fungi. The genetic variation between ten different E. pisi isolates collected from topographically distinct mountainous areas was studied using random amplified polymorphic (RAPD). Based on its morphological characteristics, the powdery mildew fungus presented high similarities to E. pisi . Molecular characterization of the ITS rDNA of E. pisi produced 650 bp nucleotides, PMITS (powdery mildew-internal transcribed region) primers produced 700 bp nucleotides, and an Erysiphe specific ITS primer pair amplified and synthesized 560 bp nucleotides. According to the findings, the collected E. pisi strains exhibited a low level of genetic diversity and only a slight differential in virulence on the host. In the study, E. pisi isolates from Anumapuram, Emerald Valley, Indira Nagar, and Thuneri showed a greater disease incidence in the natural field conditions and shared the same genetic lineage with other isolates in UPGMA hierarchical cluster analysis based on RAPD markers. There was no evidence of a link between the occurrence of the disease and these grouped populations.

The influence of nutrition and environment on human health has been known for ages. Phytonutrients (7,000 flavonoids and phenolic compounds; 600 carotenoids) and pro-health nutrients-nutraceuticals positively add to human health and may prevent disorders such as cancer, diabetes, obesity, cardiovascular diseases, and dementia. Plant-derived bioactive metabolites have acquired an imperative function in human diet and nutrition. Natural phytochemicals affect genome expression (nutrigenomics and transcriptomics) and signaling pathways and act as epigenetic modulators of the epigenome (nutri epigenomics). Transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics are some of the main platforms of complete omics analyses, finding use in functional food and nutraceuticals. Now the recent advancement in the integrated omics approach, which is an amalgamation of multiple omics platforms, is practiced comprehensively to comprehend food functionality in food science., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pandita and Pandita.)

Abscisic acid (ABA) is a plant growth regulator known for its functions, especially in seed maturation, seed dormancy, adaptive responses to biotic and abiotic stresses, and leaf and bud abscission. ABA activity is governed by multiple regulatory pathways that control ABA biosynthesis, signal transduction, and transport. The transport of the ABA signaling molecule occurs from the shoot (site of synthesis) to the fruit (site of action), where ABA receptors decode information as fruit maturation begins and is significantly promoted. The maximum amount of ABA is exported by the phloem from developing fruits during seed formation and initiation of fruit expansion. In the later stages of fruit ripening, ABA export from the phloem decreases significantly, leading to an accumulation of ABA in ripening fruit. Fruit growth, ripening, and senescence are under the control of ABA, and the mechanisms governing these processes are still unfolding. During the fruit ripening phase, interactions between ABA and ethylene are found in both climacteric and non-climacteric fruits. It is clear that ABA regulates ethylene biosynthesis and signaling during fruit ripening, but the molecular mechanism controlling the interaction between ABA and ethylene has not yet been discovered. The effects of ABA and ethylene on fruit ripening are synergistic, and the interaction of ABA with other plant hormones is an essential determinant of fruit growth and ripening. Reaction and biosynthetic mechanisms, signal transduction, and recognition of ABA receptors in fruits need to be elucidated by a more thorough study to understand the role of ABA in fruit ripening. Genetic modifications of ABA signaling can be used in commercial applications to increase fruit yield and quality. This review discusses the mechanism of ABA biosynthesis, its translocation, and signaling pathways, as well as the recent findings on ABA function in fruit development and ripening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gupta, Wani, Razzaq, Skalicky, Samantara, Gupta, Pandita, Goel, Grewal, Hejnak, Shiv, El-Sabrout, Elansary, Alaklabi and Brestic.)

Objective: During the coronavirus disease 2019 pandemic, as a safety-net organization with a substantial percentage of patients of color and with limited English proficiency (LEP), we were wary of furthering health disparities in our community. We analyzed gaps in telemedicine (telephone and video) delivery in our communities, quantified the effects of our tests of change, and began the process of accumulating evidence to create a road map for other organizations., Methods: We leveraged Lean problem-solving strategies to identify modifiable gaps across multiple domains that could inhibit equity in telemedicine. We implemented tests of change across domains of community engagement, technology, education, and access. We observed the proportion of telemedicine encounters across races and languages between April and November, 2020. Regression analyses tested the impact of race and language on telemedicine controlling for age, gender, insurance, and time., Results: Several rounds of changes and enhancements were associated with changes in telemedicine use of +5.5% ( p  < 0.0001) for Hispanic, +4.0% ( p  < 0.0001) for Spanish-speaking, -2.1% for Black ( p  < 0.05), and -4.4% for White patients ( p  < 0.001). African-American, Hispanic, and non-English-speaking patients had between 2.3 and 4.6 times the odds of preferring telephone to video encounters ( p  < 0.0001), with increases in preferences for video use over time ( p  < 0.05)., Conclusion: Our roadmap to improve equitable delivery of telemedicine was associated with a significant improvement in telemedicine use among certain minority populations. Most populations of color used telephone more often than video. This preference changed over time and with equity-focused changes in telemedicine delivery., Competing Interests: None declared., (Thieme. All rights reserved.)

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3 ± 0.34 °C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: Triple-Negative Breast Cancer (TNBC) is the most aggressive form of Breast Cancer (BC), with high rates of metastasis and recurrence and limited treatment options. Chemotherapy and radiotherapy, for example, have several harmful side effects, and no FDA-approved therapies are currently available. Repurposing old clinically approved drugs to target various TNBC targets is a novel method that has fewer side effects and leads to successful, low-cost drug development in a shorter amount of time. Medicinal plants containing various phytoconstituents (flavonoids, alkaloids, phenols, essential oils, tannins, glycosides, lactones) play a very crucial role in combating various types of diseases and are used in the drug development process because of having lesser side effects., Objective: The present review summarizes various categories of repurposed drugs that target multiple targets of TNBC, as well as phytochemical categories that target TNBC singly or in combination with old synthetic drugs., Methods: Literature information was collected from various databases such as Pubmed, Web of Science, Scopus, and Medline to understand and clarify the role and mechanism of repurposed synthetic drugs and phytoconstituents against TNBC by using keywords like "breast cancer", "repurposed drugs", "TNBC" and "phytoconstituents"., Results: Various repurposed drugs and phytochemicals that target different signaling pathways and exert their cytotoxic activities on TNBC cells ultimately lead to cell apoptosis, reducing the recurrence rate and stopping the metastasis process., Conclusion: Inhibitory effects can be seen at various levels, providing information and evidence to researchers in the drug development process. As a result, more research and investigations are needed to develop better therapeutic treatment options for TNBC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The concept of tissue engineering involves regeneration and repair of damaged tissue and organs using various combinations of cells, growth factors and scaffolds. The extracellular matrix (ECM) forms the integral part of the scaffold to induce cell proliferation thereby leading to new tissue formation. Decellularization technique provides decellularized ECM (dECM), free of cells while preserving the in vivo biomolecules. In this review, we focus on the detailed methodology of diverse decellularization techniques for various organs of different animals, and the biomedical applications employing the dECM. A culmination of different methods of decellularization is optimized, which offers a suitable microenvironment mimicking the native in vivo topography for in vitro organ regeneration. A detailed assessment of the dECM provides information on the microarchitecture, presence of ECM proteins, biocompatibility and cell proliferation. dECM has also been processed as scaffolds and drug-delivery vehicles, and utilized for regeneration.

Objective: Ensuring an efficient response to COVID-19 requires a degree of inter-system coordination and capacity management coupled with an accurate assessment of hospital utilization including length of stay (LOS). We aimed to establish optimal practices in inter-system data sharing and LOS modeling to support patient care and regional hospital operations., Materials and Methods: We completed a retrospective observational study of patients admitted with COVID-19 followed by 12-week prospective validation, involving 36 hospitals covering the upper Midwest. We developed a method for sharing de-identified patient data across systems for analysis. From this, we compared 3 approaches, generalized linear model (GLM) and random forest (RF), and aggregated system level averages to identify features associated with LOS. We compared model performance by area under the ROC curve (AUROC)., Results: A total of 2068 patients were included and used for model derivation and 597 patients for validation. LOS overall had a median of 5.0 days and mean of 8.2 days. Consistent predictors of LOS included age, critical illness, oxygen requirement, weight loss, and nursing home admission. In the validation cohort, the RF model (AUROC 0.890) and GLM model (AUROC 0.864) achieved good to excellent prediction of LOS, but only marginally better than system averages in practice., Conclusion: Regional sharing of patient data allowed for effective prediction of LOS across systems; however, this only provided marginal improvement over hospital averages at the aggregate level. A federated approach of sharing aggregated system capacity and average LOS will likely allow for effective capacity management at the regional level., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas., Scope and Approach: This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions: Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. Possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work., (Copyright © 2021 Elsevier B.V. All rights reserved.)

From time immemorial, humans have exploited plants as a source of food and medicines. The World Health Organization (WHO) has recorded 21,000 plants with medicinal value out of 300,000 species available worldwide. The promising modern "multi-omics" platforms and tools have been proven as functional platforms able to endow us with comprehensive knowledge of the proteome, genome, transcriptome, and metabolome of medicinal plant systems so as to reveal the novel connected genetic (gene) pathways, proteins, regulator sequences and secondary metabolite (molecule) biosynthetic pathways of various drug and protein molecules from a variety of plants with therapeutic significance. This review paper endeavors to abridge the contemporary advancements in research areas of multi-omics and the information involved in decoding its prospective relevance to the utilization of plants with medicinal value in the present global scenario. The crosstalk of medicinal plants with genomics, transcriptomics, proteomics, and metabolomics approaches will be discussed.

The potential of albumin-coated hollow mesoporous silica nanoparticles (A-HMSNs) to optimize the chemotherapeutic efficacy of docetaxel (DTX) was explored. The synthesized A-DTX-HMSNs had a nanometric size range, offered large surface area with numerous pores, and offered high drug entrapment and loading, that is, 79.18% ± 1.4% and 19.11% ± 1.30%, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry studies confirmed drug loading and the presence of albumin onto the developed systems, and the drug release followed Higuchi profile. A-HMSNs significantly enhanced the pharmacokinetic profile of DTX by eightfold vis-à-vis the pure DTX. The enhanced plasma levels ( C max , T max , area under the curve), prolonged drug release, long circulation time, lower clearance, hemocompatability, and substantially higher drug loading offered by these nanocarriers inherit promise of a safer and efficacious formulation of DTX.

Objectives: The ayurvedic literature reports that Dalbergia sissoo , a common medicinal plant for gastric and skin problems, has brain-revitalizing effects. However, the neuroprotective effect of this herb on an amyloid-β (Aβ) 1-42 model of Alzheimer's disease (AD) is yet unknown. The current study describes the protective effect of ethanolic extracts of D. sissoo leaves (EEDS) against Aβ (1-42)-induced cognitive deficit, oxidative stress, and neuroinflammation in rats., Materials and Methods: EEDS (300 and 500 mg/kg) was orally administered to rats for 2 weeks prior to intracerebroventricular Aβ (1-42) treatment. The neuroprotective effect of EEDS was assessed by evaluating behavioral, biochemical, and neuroinflammatory parameters in the rat hippocampus. Memory function was assessed via the Morris water maze (MWM) task 2 weeks after Aβ (1-42) administration. After 3 weeks, surgery was performed, all biochemical parameters were evaluated, and histopathological examination of the tissues was carried out., Results: EEDS improved the cognitive ability of Aβ (1-42)-administered rats in the MWM task. It reduced oxidative stress by significantly decreasing nitrite and malondialdehyde levels and increasing catalase activity and glutathione levels in the rat brain. Moreover, EEDS mitigated neuroinflammation in rats by decreasing the concentration of neuroinflammatory markers in a dose-dependent manner., Conclusion: D. sissoo leaf extract has a beneficial role in alleviating cognitive deficits in AD by modulating cholinergic function, oxidative stress, and neuroinflammation.

Background: Several health problems, especially musculoskeletal disorders, are caused by differences in work cultures and human lifestyles around the world. While the conventional approach to treating such conditions emphasizes a balanced work-life and daily exercise, nutraceuticals have proven to be successful. Nutraceuticals are dietary compounds that help sustain cartilage metabolism homeostasis, reducing articular pain. Dietary intake of a variety of nutraceuticals is thought to be essential for controlling and, more specifically, preventing osteoarthritis and osteoporosis., Objective: The current article offers a succinct overview in which data was gathered and searched using specific key terms related to nutraceuticals, osteoarthritis, and osteoporosis that were available in public domains for analysis and evaluation., Methods: The current write-up offers a concise summary of disease and its relevance as to how nutraceuticals are helpful, based on the defined findings and their interpretation. The present review also discusses the existing literature, patents, and current studies in the era of nutraceuticals for osteoarthritis and osteoporosis treatment, offering a rational basis for further investigation and research., Result: This article discusses a wide variety of nutraceuticals with possible uses for osteoarthritis and osteoporosis patients. An analysis revealed that nutraceuticals' efficacy has been established. However, further study and investigation are needed to determine their protection., Conclusion: As a result of this analysis, it was concluded that more innovation and technology transfer were required. It was also concluded that greater industry-academic collaboration was required to begin more effective research in the treatment of osteoarthritis and osteoporosis with nutraceuticals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Methotrexate (MTX) is the first line of choice for the management of rheumatoid arthritis (RA) and has been reported for its low bioavailability and side effects. Combination therapy has been widely investigated to overcome bioavailability issues and to reduce adverse effects associated with monotherapy. Various phytoconstituents such as resveratrol (RSV) and curcumin have been found to possess potent anti-inflammatory activity via downregulating the signaling of cytokines (interleukin [IL]-1, IL-6, and tumor necrosis factor alpha) and nuclear factor kappa B signaling. The prime objective of this study was to develop transdermal gel containing MTX-RSV loaded nanoemulsions (NEs) to overcome bioavailability issues and adverse effects of RA monotherapy. The NEs optimized by using Box-Behnken Design were incorporated within gel , and an in vitro skin permeation study performed on rat skin by using vertical Franz diffusion cells exhibited controlled drug release up to 48 h. Subsequently, anti-inflammatory and potential anti-arthritic activities of the combination in nanocarrier were assessed in rats and showed 78.76 ± 4.16% inhibition in inflammation and better anti-arthritic effects. Consequently, integration of dual delivery with nanotechnology can hopefully produce successful therapeutic options for rheumatic diseases.

The aim of present study was to develop folate receptor targeted lipoprotein-mimetic nanoparticles of resveratrol (RSV). Lipoprotein-mimicking nanocarrier (RSV-FA-LNPs) comprising of phosphatidyl choline, cholesterol, stearyl amine and folic acid-tagged bovine serum albumin (FA-BSA) were prepared. Folic acid was conjugated to bovine serum albumin by amide bond at a binding rate of 9.46 ± 0.49 folate molecules per bovine serum albumin. The particle size and entrapment efficiency of the developed nanoparticles was found to be 291.37 ± 3.81 nm and 91.96 ± 1.83%, respectively. The in vitro release study depicted that developed nanocarrier prolonged the drug release till 72 h in phosphate buffer saline (pH 7.4). The anticancer potential of RSV in case of RSV-FA-LNPs was found to be substantially improved against MCF-7 cells overexpressing folate receptors compared to non-targeted nanoparticles. The pharmacokinetics studies after intravenous administration in healthy Wistar rats depicted that lipoprotein mimicking nanoparticles presented the longer circulation time (>48 h) compared to free drug which disappeared in few hours (6 h). The in vitro and preclinical findings of the present study demonstrated the applicability of lipoprotein mimicking nanocarriers for the safer and effective delivery of bioactives., 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 © 2020 Elsevier B.V. All rights reserved.)

Paclitaxel loaded lipid-polymer nanoparticles (NPs) were successfully synthesized using poly lactide-co-glycolide (PLGA) as polymer and stearyl amine, soya lecithin as lipids via single step nanoprecipitation method. The study was aimed to combine the advantage of structural integrity of hybrid NPs containing PLGA core and lipid in the shell. Surfactants such as polyvinyl alcohol (PVA), tocopheryl polyethylene glycol succinate (TPGS), pluronic 68 (F68) and human serum albumin (HSA) were used as stabilizers. NPs were characterized w.r.t. morphology, particle size, zeta potential, encapsulation efficiency, in vitro drug release, protein binding capability and blood compatibility. NPs were in size range of 150-400 nm and the particle size was greatly influenced by type and concentration of surfactants and lipids. TEM analysis confirmed the spherical shape and coating of the lipid on the NPs surface. Highest percentage entrapment efficiency was observed in NPs prepared with HSA as surfactant. The release rate of paclitaxel from modified NPs was much slower as compared to unmodified NPs. The percent protein binding of P-PVA, P-TPGS, P-F68 and P-HSA (unmodified NPs) was found to be 15.11%, 16.27%, 27.90% and 33.72%, respectively demonstrating effect of surface properties of NPs on protein binding. The hemolytic activity of the NPs was found to be dependent on type of surfactant and not on the lipid employed. PVA, TPGS, F68, HSA surfactants showed ~16%, ~10%, ~13%, ~7% hemolysis rate, respectively. The surface nature of NPs had a significant effect on the circulation profile of formulations. The HSA based NPs showed prolonged blood circulation time when compared to NPs without lipid coating. Thus, the synthesized dual lipid coated PLGA NPs with HSA could act as a potential nano-system for controlled delivery of paclitaxel., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Peroxisome proliferator-activated receptor (PPAR) δ is expressed universally in the entire tissues, particularly in those concerned with the lipid metabolism. PPAR δ stimulation alters body's energy fuel preference to fat from glucose and shows up as an emerging pharmacological target for the treatment of metabolic disorders., Methods: A new series of cinnamic acid derivatives was synthesized and evaluated for the antidiabetic and antiinflammatory activities in the animal models followed by in silico docking studies to determine the binding interactions for the best fit conformations in the binding site of the PPARδ protein., Results: Amongst the synthesized molecules, compound 3 showed higher antidiabetic activity in oral glucose tolerance test and compound 1 showed higher antiinflammatory activity in the carrageenan induced rat paw oedema method. The in vivo study results were supported by the similar in silico molecular docking results. Most of the synthesized derivatives showed drug likeness as depicted via Lipinski's rule of 5., Conclusion: These molecules can serve as the early hit molecules for the discovery of safe, effective and bioavailable PPARδ agonists for the potential treatment of various metabolic disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Resveratrol (RSV) has shown to possess anti-cancer potential in various studies; however, its poor water solubility, extensive first-pass metabolism, and photostability issues have limited its clinical application. Therefore, the aim of the current investigation was to formulate and optimize a nanostructured lipid carriers (NLCs) based parenteral formulation of RSV for its effective delivery to breast cancer cells. NLCs loaded with RSV (RSV-NLCs) were formulated by the modified solvent injection technique and were systematically optimized using a three level-three factor Box-Behnken design. The optimized RSV-NLCs exhibited an optimum particle size of 88.3 ± 3.1 nm and high entrapment efficiency of 88.0 ± 2.6%. These optimized NLCs were further investigated for the targeting potential using folic acid as the targeting moiety and cell cytotoxicity experiments revealed high cytotoxic effects of folate modified NLCs (RSV-FA-NLCs) compared to unmodified NLCs on MCF-7 cells with high levels of over-expressed folate receptors suggesting the high potential of targeted NLCs in enhancing the therapeutic concentration of RSV to breast cancer cells. In vivo pharmacokinetic studies demonstrated a nine-fold increase in AUC values obtained with RSV-FA-NLCs (57.92 ± 4.15 μg h/mLh) in comparison to free RSV (6.37 ± 1.16 μg h/mLh). The promising results from this investigation corroborated the tremendous potential of lipidic nanocarriers in augmenting the therapeutic potential of RSV., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Aegle marmelos (L.) Correa (A. marmelos) has been used in Ayurvedic medicine as a brain tonic however its neuroprotective effect against streptozotocin (STZ) induced cognitive impairment and oxidative stress has not been reported yet in vivo. Therefore, the present study was attempted to investigate the neuroprotective potential of ethanolic extract of A. marmelos leaves (AME) on STZ induced memory impairment in male rats., Main Methods: Albino Wistar rats were pre-treated orally with AME at the doses 200 and 400 mg/kg for two weeks, followed by intracerebroventricular (i.c.v.) injection of STZ (3 mg/kg) on day 1 and 3. Two weeks after STZ administration, behavioural parameters were monitored using Morris water maze task. Biochemical and histopathological studies were carried out after three weeks of STZ administration. The levels of oxidative stress markers (malondialdehyde (MDA), glutathione, nitrite, catalase) neuroinflammatory mediators; tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and acetylcholinesterase (AChE) activity were estimated in hippocampus of rat brain. Donepezil (5 mg/kg) was taken as a standard drug., Key Findings: The levels of MDA, nitrite, TNF-α and IL-6 were significantly increased while glutathione levels were significantly decreased in hippocampus of STZ-treated rats. Further, a significant decrease in the activity of catalase and increase in AChE activity was observed indicating cholinergic hypofunction and neuronal damage in STZ-treated animals. All these alterations were significantly ameliorated by AME in a dose dependent manner., Significance: The neuroprotective potential of A. marmelos against STZ induced oxidative stress and cognitive deficit in rats indicates its therapeutic value in Alzheimer's disease (AD)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), PDE superfamily members, increase inflammatory processes in immunomodulatory as well as pro-inflammatory cells via breakdown of cyclic adenosine monophosphate. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates which can regulate pro-inflammatory as well as T-cell function and can be particularly advantageous in the treatment of a wide-ranging disorders associated with the immune system as well as inflammatory diseases with fewer unwanted adverse effects., Objective: The current research work was planned to design and synthesize some newer substituted 1,3- thiazolidine-2,4-dione derivatives as dual inhibitors of PDE4 and PDE7 followed by evaluation of their anti-inflammatory activity and in silico docking studies., Methods: A new series of substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized followed by evaluation of their anti-inflammatory activity in animal models. In silico docking studies were performed for the evaluation of the binding pattern of synthesized derivatives in the binding site of both PDE4 and PDE7 proteins., Results: Amongst the newly synthesized derivatives, compounds 5 and 12 showed higher antiinflammatory activity in the animal model. The results of in vivo animal studies were found to be in concordance with the results of molecular docking studies., Conclusion: These newly synthesized derivatives can act as the lead molecules for the design of safe and therapeutically effective agents for various inflammatory diseases acting via inhibition of both PDE4 and PDE7., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Glucokinase (GK) is the main enzyme which controls the blood glucose levels in a safe and narrow physiological range in humans. GK activators are the novel type of therapeutic agents which act on GK enzyme and show their anti-diabetic potential. The present work was planned to synthesize and evaluate the antidiabetic potential of a new series of thiazole-2-yl benzamide derivatives as potential GK activators. A series of thiazole-2-yl benzamide derivatives were synthesized from benzoic acid and evaluated by in vitro enzymatic assay for GK activation. In silico docking studies were carried out to determine the binding interactions for the best fit conformations in the allosteric site of GK enzyme. Based on the results of in vitro enzyme assay and in silico studies, the selected molecules were tested for their antidiabetic activity in the oral glucose tolerance test (OGTT). The results of the in vitro enzymatic assay were found to be in accordance to that of in silico studies. Amongst the synthesized molecules, compounds 1, 2, 5 and 8 displayed good in vitro GK activation (activation fold between 1.48 and 1.83). Compounds 2 and 8 exhibited highest antidiabetic activity in OGTT studies. The results of the in vivo antidiabetic studies were found to be in parallel to that of docking and in vitro studies. These newly synthesized thiazol-2-yl benzamide derivatives thus can be treated as the initial hits for the development of new, safe, effective and orally bioavailable GK activators as therapeutic agents for the treatment of type 2 diabetes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Breast cancer is the second-leading cause of death in women worldwide owing to aggressive metastasis, lack of early diagnosis and poor access to treatment amenities. During the past decade, mesoporous silica nanoparticles (MSNs) have gained ground for the delivery of a wide variety of chemotherapeutic and bioimaging agents owing to their unique characteristics and straightforward fabrication methods. Present research studies based on MSNs have provided various potential insights in their applicability in breast cancer treatment by improving solubility and stability and decreasing the adverse effects of current treatment regimens. This review focuses on the applicability of this novel modality in the management of breast cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Phosphodiesterase 4 (PDE4), is one of the members of PDE superfamily which catalyzes the hydrolysis of cyclic adenosine monophosphate to adenosine monophosphate in pro-inflammatory and immunomodulatory cells, leading to increased inflammatory processes. PDE4 has been reported as an attractive therapeutic target involved in various inflammatory disorders., Objective: The present work was designed to synthesize and evaluate the anti-inflammatory activity of some new triazole amine derivatives as potential PDE4 inhibitors., Method: The present work involved the synthesis of a series of newer substituted triazole amine derivatives followed by characterization using FTIR and 1H-NMR spectroscopy and their in silico evaluation by docking studies to determine the binding interactions for the best fit conformations in the binding site of PDE4 protein. Based on the results of the in silico studies, the selected compounds were tested for the anti-inflammatory activity using carrageenan-induced paw oedema method., Results: The yields of synthesized compounds were moderate and amongst the synthesized molecules, compound 5 demonstrated high anti-inflammatory activity. The results of experimental studies were found to be in concordance with that of the in silico docking results. Most of the synthesized molecules were also found to possess drug like properties as contrived by Lipinski's rule of five., Conclusion: These newly synthesized molecules could act as the starting hits for the design of effective, potent and selective PDE4 inhibitors for the promising treatment of inflammatory disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)