Effect of Vitamin D on Retinoblastoma Protein in Prediabetic Individuals.

About 50.8 million people were diagnosed with diabetes in 2011; the count has increased by 10 million in the last five years. Type-1 diabetes could occur at any age, but predominantly in children and young adults. The risk of developing type II diabetes mellitus in the offspring of parents with DM II is 40% if one parent has DM II and approaches 70% if both parents have DM II. The process of developing diabetes from normal glucose tolerance is continuous, with insulin resistance being the first stage. As prediabetes progresses slowly to DM II, it may take approximately 15-20 years for an individual to become diabetic. This progression can be prevented or delayed by taking some precautions and making some lifestyle amendments, e.g., reducing weight by 5-7% of total body weight if obese, etc. Retinoblastoma protein is one of the pocket proteins that act as crucial gatekeepers during the G1/S transition in the cell cycle. A loss or defect in single- cell cycle activators (especially CDK4 and CDK6) leads to cell failure. In diabetic or stress conditions, p53 becomes a transcription factor, resulting in the transactivation of CKIs, which leads to cell cycle arrest, cell senescence, or cell apoptosis. Vitamin D affects insulin sensitivity by increasing insulin receptors or the sensitivity of insulin receptors to insulin. It also affects peroxisome proliferator-activated receptors (PPAR) and extracellular calcium. These influence both insulin resistance and secretion mechanisms, undertaking the pathogenesis of type II diabetes. The study confines a marked decrement in the levels of random and fasting blood glucose levels upon regular vitamin D intake, along with a significant elevation of retinoblastoma protein levels in the circulatory system. The most critical risk factor for the occurrence of the condition came out to be family history, showing that patients with first-degree relatives with diabetes are more susceptible. Factors such as physical inactivity or comorbid conditions further aggravate the risk of developing the disease. The increase in pRB levels caused by vitamin D therapy in prediabetic patients directly influences blood glucose levels. pRB is supposed to play a role in maintaining blood sugar levels. The results of this study could be used for further studies to evaluate the role of vitamin D and pRB in regeneration therapy for beta cells in prediabetics.

Exploring research trends and focal points in the application of transcranial magnetic stimulation for enhancing motor function in post-stroke patients: A bibliometric and content analytical approach.

BACKGROUND: Motor impairment is a significant health concern among post-stroke patients. Transcranial magnetic stimulation (TMS) is considered as an emerging rehabilitation therapy for various neurological conditions, and the effects of excitatory TMS on post-stroke have received much attention in past decade. However, the future hotspots and content analysis on the growth trends have not been studied. This bibliometric and content analysis aimed to study the global developmental history and current status of TMS for motor function of post-stroke from January 2004 to July 2023. METHODS: Literature published on Scopus database from January 2004 to July 2023 were searched. Extracted data was analysed using the R studio and VOS viewer for author's publication, institutions, sources, keyword co-occurrence and world network analysis. Keyword cluster analysis, co-citation analysis for references and content analysis were also performed. We screened top 10 most cited or collaborative areas for publications, institutions and sources in the field of TMS associated with motor function of post-stroke. RESULTS: In this study, a comprehensive analysis of 267 publications was conducted, revealing a substantial surge in research output throughout 2022. China emerged as the leading contributor, with 409 publications, followed by the United States with 211 publications. Notably, Harvard Medical School stood out as one of the most prolific institutions, accounting for 34 publications (13.12 %). Among researchers, Abo M garnered the highest publication count, with 9 articles (14.5 %). The Word cloud showed that motor function, repetitive transcranial magnetic stimulation (rTMS) and upper limb have been the focus of recent attention. Burst keywords on thematic evolution and topic trend shows that quality of life scale, network parameters, cognition, lower limb motor function are the future trends. CONCLUSION: This bibliometric study describes that TMS has shown promising results in improving motor function of upper extremity in stroke patients, the long-term effects and durability of these improvements are still being investigated. Future research might focus on understanding the optimal duration and frequency of TMS sessions for sustained motor recovery and exploring strategies to maintain gains achieved through TMS over extended periods of time. Future studies can investigate the changes in the lower limb motor function.

Ring Expansion of Isatins via 1,2-Phospha-Brook Rearrangement: A Route to the Synthesis of 2-Quinolinone-Derived p-Quinone Methides.

A Lewis acid-mediated one-carbon homologation approach to installing a 2-quinolinone core embedded with para-quinone methides, in a high yield of up to 92%, and with high regioselectivity has been developed. Also, post-synthetic modifications, including C-P, C-S, and C-C bond formations, have been demonstrated by the 1,6-addition of suitable nucleophiles. Further, cyclopropanation of 2-quinolinone-embedded p-QM is also demonstrated affording a contiguous quaternary spiro center.

A Survey of Soft Computing Approaches in Biomedical Imaging.

Medical imaging is an essential technique for the diagnosis and treatment of diseases in modern clinics. Soft computing plays a major role in the recent advances in medical imaging. It handles uncertainties and improves the qualities of an image. Until now, various soft computing approaches have been proposed for medical applications. This paper discusses various medical imaging modalities and presents a short review of soft computing approaches such as fuzzy logic, artificial neural network, genetic algorithm, machine learning, and deep learning. We also studied and compared each approach used for other imaging modalities based on the certain parameter used for the system evaluation. Finally, based on comparative analysis, the possible research strategies for further development are proposed. As far as we know, no previous work examined this issue.

Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations.

Coronavirus Disease 19 (COVID-19), due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become an on-going global health emergency affecting over 94 million cases with more than 2 million deaths globally. Primarily identified as atypical pneumonia, it has developed into severe acute respiratory distress syndrome (ARDS), a multi-organ dysfunction with associated fatality. Ever since its emergence, COVID-19 with its plethora of clinical presentations has signalled its dynamic nature and versatility of the disease process. Being a disease with droplet transmission has now assumed the proportion of a suspected airborne nature which, once proved, poses a Herculean task to control. Because of the wide distribution of the human angiotensin-converting enzyme-2 (hACE2) receptors, known for its transmission, we envisage its multiorgan spread and extensive disease distribution. Thus, an extensive review of the extrapulmonary organotropism of SARS-CoV-2 with organ-specific pathophysiology and associated manifestations like dermatological complications, myocardial dysfunction, gastrointestinal symptoms, neurologic illnesses, hepatic and renal injury is needed urgently. The plausible mechanism of site-specific viral invasion is also discussed to give a comprehensive understanding of disease complexity, to help us to focus on research priorities and therapeutic strategies to counter the disease progression. A note on the latest advancements in vaccine research will enlighten the scientific world and equip it for better preparedness.

CT Image Reconstruction Using NLMfuzzyCD Regularization Method.

Aims and Scope: Computed tomography (CT) is one of the most efficient clinical diagnostic tools. The main goal of CT is to reproduce an acceptable reconstructed image of an object (either anatomical or functional behaviour) with the help of a limited set of projections at different angles. BACKGROUND: To achieve this goal, one of the most commonly iterative reconstruction algorithm called Maximum Likelihood Expectation Maximization (MLEM) is used. OBJECTIVE: The conventional Maximum Likelihood (ML) algorithm can achieve quality images in CT. However, it still suffers from optimal smoothing as the number of iterations increases. METHODS: For solving this problem, this paper presents a novel statistical image reconstruction algorithm for CT, which utilizes a nonlocal means of fuzzy complex diffusion as a regularization term for noise reduction and edge preservation. RESULTS: The proposed model was evaluated on four test cases phantoms. CONCLUSION: Qualitative and quantitative analyses indicate that the proposed technique has higher efficiency for computed tomography. The proposed method yields significant improvements when compared with the state-of-the-art techniques.

Antiaflatoxigenic effects of selected antifungal peptides.

Aflatoxins are potent carcinogenic mycotoxins produced as secondary metabolites mainly by the fungi Aspergillus flavus and Aspergillus parasiticus. Control measures to curtail the contamination of aflatoxin in food products is still a challenge. Although there are several reports on the antifungal peptides, there is no specific study on the action of antifungal peptides on aflatoxin synthesis. This work details the effect of four antimicrobial peptides (AMPs) - PPD1 (FRLHF), 66-10 (FRLKFH), 77-3 (FRLKFHF) and D4E1 (FKLRAKIKVRLRAKIKL) on the aflatoxin production by A. flavus and A. parasiticus. Results of the investigations suggests that AMPs at near minimum inhibitory concentrations (MIC) were effectively inhibiting aflatoxins, without hindering the growth of the fungi. These AMPs, at concentrations near MIC, induced membrane permeabilisation, without inducing cellular leakage. The involvement of oxidative stress for the aflatoxin synthesis was reversed by the antioxidant nature of the peptides as evidenced by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay, reactive oxygen species production, malondialdehyde and antioxidant enzymes analysis. Quantitative real time polymerase chain reaction (RT-qPCR) analysis of the aflatoxin gene cluster showed that 'aflR' and its downstream genes expressions were significantly down regulated. Conidiation of the fungi were negatively influenced by the peptides as evidenced by scanning electron microscopy analysis and RT-qPCR. mRNA levels of Manganese-superoxide dismutase (Mn-SOD) showed a decrease in the expression in RT-qPCR. The effect of these peptides on aflatoxin inhibition provides insight into their use as novel antiaflatoxigenic molecules.

A mouse protein that localizes to acrosome and sperm tail is regulated by Y-chromosome.

BACKGROUND: Acrosomal proteins play crucial roles in the physiology of fertilization. Identification of proteins localizing to the acrosome is fundamental to the understanding of its contribution to fertilization. Novel proteins are still being reported from acrosome. In order to capture yet unreported proteins localizing to acrosome in particular and sperm in general, 2D-PAGE and mass spectrometry analysis of mouse sperm proteins was done. RESULTS: One of the protein spots identified in the above study was reported in the NCBI database as a hypothetical protein from Riken cDNA 1700026L06 that localizes to chromosome number 2. Immunofluorescence studies using the antibody raised in rabbit against the recombinant protein showed that it localized to mouse acrosome and sperm tail. Based on the localization of this protein, it has been named mouse acrosome and sperm tail protein (MAST, [Q7TPM5 (http://www.ncbi.nlm.nih.gov/protein/Q7TPM5)]). This protein shows 96% identity to the rat spermatid specific protein RSB66. Western blotting showed that MAST is expressed testis-specifically. Co-immunoprecipitation studies using the MAST antibody identified two calcium-binding proteins, caldendrin and calreticulin as interacting partners of MAST. Caldendrin and calreticulin genes localize to mouse chromosomes 5 and 8 respectively. In a Yq-deletion mutant mouse, that is subfertile and has a deletion of 2/3rd of the long arm of the Y chromosome, MAST failed to localize to the acrosome. Western blot analysis however, revealed equal expression of MAST in the testes of wild type and mutant mice. The acrosomal calcium-binding proteins present in the MAST IP-complex were upregulated in sperms of Yq-del mice. CONCLUSIONS: We have identified a mouse acrosomal protein, MAST, that is expressed testis specifically. MAST does not contain any known motifs for protein interactions; yet it complexes with calcium-binding proteins localizing to the acrosome. The misexpression of all the proteins identified in a complex in the Yq-del mice invokes the hypothesis of a putative pathway regulated by the Y chromosome. The role of Y chromosome in the regulation of this complex is however not clear from the current study.

Angiogenic response of advanced glycation end products (AGEs) involves PPARgamma.

Diabetes is associated with increased formation of advanced glycation end products (AGEs), which have been implicated in micro and macrovascular complications of diabetes. Our earlier reports showed proangiogenic effect of AGE-bovine serum albumin (BSA). In order to understand the mechanism of AGE-mediated angiogenesis, the possibility of involvement of peroxisome prolifeator activated receptor (PPAR) gamma, a ligand activated transcription factor was examined. The angiogenic effect was studied in chick chorio allantoic membrane (CAM) and by analyzing angiogenic markers in human umbilical vein endothelial cells (HUVECs) in culture. The involvement of PPAR y was investigated using synthetic PPAR gamma agonist GW 1929 and antagonist GW 9662 and by RT-PCR. In CAM assay, PPAR gamma antagonist GW 9662 reversed the AGE-induced effect on vascularity. In HUVECs in culture, GW 9662 reversed the effect of AGE-BSA and decreased the expression of CD 31, E-Selectin and VEGF. RT-PCR analysis showed that treatment with AGE-BSA caused upregulation of PPAR gamma mRNA levels. The reversal of the effect of AGE on angiogenesis by treatment with PPAR gamma antagonists and up-regulation of PPAR gamma gene in HUVECs treated with AGE-BSA suggested the possible involvement of PPAR gamma-dependent downstream pathway in mediating the angiogenic effect of AGE.

Differential modulation of angiogenesis by advanced glycation end products.

Divergent angiogenic responses occur in different organs in a diabetic state. Many of the pathological effects were mediated by the advanced glycation end products (AGEs) of non-enzymatically glycated molecules. Investigations were carried out using different angiogenic model systems to examine whether the angiogenic response to AGEs is influenced by the cellular microenvironment. AGE-albumin increased angiogenesis in chick chorioallantoic membrane (CAM). It also increased sprouting in rat aortic rings and the expression of angiogenic markers CD31 and E-selectin and the angiogenic growth factor, vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs) in culture, suggesting a proangiogenic effect. But in a serum-supplemented condition, AGE-albumin inhibited aortic sprouting and expression of angiogenic markers and VEGF production by HUVECs, suggesting an antiangiogenic effect in the presence of serum. Blocking of the AGE effect by the antioxidants, N-acetyl cysteine and ascorbic acid, suggested that the AGE effect involved oxidant stress. Reversal of the AGE effect by LY 294 002, an inhibitor of the Akt pathway and increased phosphorylation of Akt in cells maintained in serum-free medium, suggested the involvement of the Akt pathway in mediating the AGE effect; such an effect was absent in a serum-supplemented condition. These opposing effects of AGE-albumin on angiogenesis in the presence and absence of serum suggested that the AGE accumulated in a hyperglycemic condition can affect angiogenesis depending on the microenvironment of the cells.