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Siddhartha Dutta,1 Rima B Shah,1 Shubha Singhal,1 Sudeshna Banerjee Dutta,2 Sumit Bansal,3 Susmita Sinha,4 Mainul Haque5 1Department of Pharmacology, All India Institute of Medical Sciences, Rajkot, Gujarat, India; 2Department of Medical Surgical Nursing, Shri Anand Institute of Nursing, Rajkot, Gujarat, India; 3Department of Anesthesiology, All India Institute of Medical Sciences, Rajkot, Gujarat, India; 4Department of Physiology, Khulna City Medical College and Hospital, Khulna, Bangladesh; 5Unit of Pharmacology, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, MalaysiaCorrespondence: Mainul Haque, Email runurono@gmail.com

Siddhartha Dutta,1 Rima B Shah,1 Shubha Singhal,1 Sudeshna Banerjee Dutta,2 Sumit Bansal,3 Susmita Sinha,4 Mainul Haque5 1Department of Pharmacology, All India Institute of Medical Sciences, Rajkot, Gujarat, India; 2Department of Medical Surgical Nursing, Shri Anand Institute of Nursing, Rajkot, Gujarat, 360005, India; 3Department of Anaesthesiology, All India Institute of Medical Sciences, Rajkot, Gujarat, India; 4Department of Physiology, Khulna City Medical College and Hospital, Khulna, Bangladesh; 5Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, 57000, MalaysiaCorrespondence: Shubha Singhal, Department of Pharmacology, All India Institute of Medical Sciences-Rajkot, Ayush Block, Khanderi, Para Pipaliya, Rajkot, Gujarat, India, Tel +91 9560372056, Email Drshubhasinghal@gmail.com Mainul Haque, Unit of Pharmacology, Faculty of Medicine and Defence Health Sciences, Universiti Pertahanan Nasional Malaysia, National Defence University of Malaysia- Kem, Perdana, Sungai Besi, Kuala Lumpur, 57000, Malaysia, Tel +60 109265543, Email runurono@gmail.comAbstract: Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.Keywords: metformin, diabetes, pleotropic effect, cancer, cardiovascular, neuroprotection, Prediabetes

Migraine, a common neurological condition, is characterized by a chronic and recurring headache that affects numerous people globally. Several drugs are available for the treatment and prophylaxis of migraine with their shortfalls. Zinc could play a role in migraine management because of its anti-inflammatory and antioxidant properties. This study was planned to systematically review the scientific databases to gather evidence regarding the role of zinc in the management of migraine. The protocol was registered with the PROSPERO (CRD42023398478). Three databases PubMed, The Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched with the keywords "migraine", "migraine disorders" and "zinc". A literature search led to the retrieval of 35 studies; of these five studies (2 clinical trials and 3 observational studies) were comprised in a systematic review. Clinical trials' risk of bias assessment is low. The review suggested a positive role of zinc in managing migraine however, the evidence requires further strengthening. The available clinical literature on the effectiveness of zinc in migraines is limited; hence, more robust and large clinical trials are required to support the role of zinc in migraines., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants ( n  = 492), 45.3% ( n  = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy., Competing Interests: Russell Kabir is an Academic Editor for PeerJ. The other authors declare that they have no competing interests., (©2024 Majumder et al.)

The role of vitamin D in maintaining gum well-being is crucial. However, scientific research reported that the connotations of cholecalciferol and periodontal health have been divested in the present literature. However, there is enormous heterogeneity in the data available. The current review aims to systematically review and appraise the available literature investigating the role of vitamin D in maintaining periodontal health. Studies included randomized controlled trials and clinical trials following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and cohort studies reporting associations between vitamin D and oral health in systemically healthy patients. Databases such as PubMed, Google Scholar, Scopus, Embase, and other sources, including hand search, were searched until May 2023 using together-equipped search sequences. Altogether, scientific articles that conform to the inclusion principles underwent a thorough eminence evaluation. All papers meeting inclusion criteria were subject to quality assessment, and the method used to assess the risk of bias was the Cochrane risk of bias tool. The search identified 1883 papers, among which 1435 were excluded after title evaluation. After abstract and title screening, 455 were excluded, and six full texts were assessed. After full-text evaluation, two articles were excluded, and only four were included. The data shows vitamin D's association with oral health maintenance. Along with its action on bone metabolism, it has extended function, which provides for its action as an anti-inflammatory agent and production of anti-microbial peptides, which help maintain oral health. Although the literature available is immense, there is enormous heterogenicity in the papers conducted to appraise the association between vitamin D and oral health. This systematic review has filtered all the data to review a few essential aspects of the role of vitamin D in maintaining oral physiology. Vitamin D has a linear relationship with periodontal health; however, the evidence is insufficient, and further studies must be done., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shah et al.)

The development of neuronal connectivity requires stabilization of dynamic axonal branches at sites of synapse formation. Models that explain how axonal branching is coupled to synaptogenesis postulate molecular regulators acting in a spatiotemporally restricted fashion to ensure branching toward future synaptic partners while also stabilizing the emerging synaptic contacts between such partners. We investigated this question using neuronal circuit development in the Drosophila brain as a model system. We report that epidermal growth factor receptor (EGFR) activity is required in presynaptic axonal branches during two distinct temporal intervals to regulate circuit wiring in the developing Drosophila visual system. EGFR is required early to regulate primary axonal branching. EGFR activity is then independently required at a later stage to prevent degradation of the synaptic active zone protein Bruchpilot (Brp). Inactivation of EGFR results in a local increase of autophagy in presynaptic branches and the translocation of active zone proteins into autophagic vesicles. The protection of synaptic material during this later interval of wiring ensures the stabilization of terminal branches, circuit connectivity, and appropriate visual behavior. Phenotypes of EGFR inactivation can be rescued by increasing Brp levels or downregulating autophagy. In summary, we identify a temporally restricted molecular mechanism required for coupling axonal branching and synaptic stabilization that contributes to the emergence of neuronal wiring specificity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We provide a perturbative scheme that is suitable to study oscillating states in driven Langevin systems in the large viscous regime. We explicitly determine the oscillating state distribution of an underdamped Brownian particle driven by a time-dependent periodic potential. Apart from the harmonic and anharmonic parameters of the potential, the noise strength and the viscous parameter (or equivalently their ratio referred to as the thermal parameter), which appear in the dynamics of the Brownian particle, are also driven periodically. We specify various nonequilibrium observables, relevant to characterize the oscillating states, and evaluate them to linear order in anharmonic perturbation. We find that the effect of viscous drives on oscillating states is measurable even at leading order and show that the thermodynamic properties of the system in these states are significantly distinct from those in equilibrium or even from those exhibited by oscillating states of overdamped driven systems.

The effective loading or encapsulation of multimodal theranostic agents within a nanocarrier system plays an important role in the clinical development of cancer therapy. In recent years, the silk fibroin protein-based delivery system has been drawing significant attention to be used in nanomedicines due to its biocompatible and biodegradable nature. In this study, silk fibroin nanoparticles (SNPs) have been synthesized by a novel and cost-effective ultrasonic atomizer-based technique for the first time. The fabricated SNPs were coencapsulated by the FDA-approved indocyanine green (ICG) dye and the chemotherapeutic drug doxorubicin (DOX). The synthesized SNPs are spherical, with an average diameter of ∼37 ± 4 nm, and the ICG-DOX-coencapsulated SNPs (ID-SNPs) have a diameter size of ∼47 ± 6 nm. For the first time, here we demonstrate that DOX helps in the higher loading of ICG within the ID-SNPs, which enhances the encapsulation efficiency of ICG by ∼99%. This could be attributed to the interaction of ICG and DOX molecules with the silk fibroin protein, which helps ICG to get loaded more efficiently within these nanoparticles. The overall finding of this study suggests that the ID-SNPs could be utilized for enhanced ICG-complemented multimodal deep-tissue bioimaging and synergistic chemo-photothermal therapy.