Overview of reemerging mpox infection with a focus on neurological manifestations.

Mpox, a reemerging zoonotic disease caused by the mpox virus, has garnered increasing attention due to its potential for severe clinical manifestations. While the cutaneous and systemic presentations of mpox have been well-documented, its neurological complications have recently emerged as an area of concern. This review provides a brief overview of the neurological aspects of mpox infection, highlighting the key findings and challenges in understanding and managing these complications. Neurological manifestations in mpox patients range from mild symptoms such as headaches and dizziness to more severe conditions, including encephalitis and seizures. The pathogenesis of neurological involvement is not yet fully elucidated but is thought to involve viral dissemination to the central nervous system. This dissemination may occur through haematogenous or neuronal routes, contributing to the diverse clinical spectrum observed. Early recognition and diagnosis of neurological complications in mpox are crucial for implementing appropriate therapeutic interventions and improving patient outcomes.

Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer.

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.

Cynaropicrin, a sesquiterpene lactone, triggers apoptotic cell death in triple negative breast cancer cells.

BACKGROUND: Breast cancer is the most common cancer in the world. Cynaropicrin is a natural sesquiterpene lactone with potential anticancer effects. The present study was conducted to evaluate the effect of cynaropicrin on proliferation and apoptosis in breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cell lines were treated with increasing concentrations of cynaropicrin. The viability of both cell lines was measured using MTT assay. Flowcytometry was used to detect apoptotic cells. The expression levels of apoptosis-related genes were determined using quantitative polymerase chain reaction. The protein expression of apoptosis markers was determined by western blotting. RESULTS: Cynaropicrin significantly diminished the proliferation of MDA-MB-231 and MCF-7 cell lines in a dose-dependent manner. Flowcytometry data uncovered that cynaropicrin augmented early and late apoptosis in MDA-MB-231 cells. Real time-PCR and western blotting results also confirmed the upregulation of pro-apoptotic Bax, caspase-3, -8, and 9 as well as downregulated level of anti-apoptotic marker Bcl-2. Cynaropicrin also remarkably increased the activity of caspase-3, -8, and 9 in MDA-MB-231 cells. However, cynaropicrin neither promoted apoptosis in MCF-7 cells nor altered the expression levels and activity of above mentioned apoptotic markers. CONCLUSION: The present data indicated anti-proliferative properties of cynaropicrin against breast cancer and highlighted apoptosis-inducing effects of this sesquiterpene on triple negative breast cancer (TNBC) cells. These data may suggest cynaropicrin as a potential anti-TNBC agent to tackle therapy resistance in this type of breast cancer.

Resistance of Nile tilapia fed with Padina boergesenii extract to Pseudomonas putida infection.

The aim of this research was to estimate the immunopotentiation effect of brown algae Padina boergesenii water extract on Nile tilapia, Oreochromis niloticus through resistance to Pseudomonas putida infection. Gas Chromatography Mass Spectrometry was utilized to characterize the seaweed phytoconstituents. One hundred and twenty-six fish were divided in triplicates into two equal groups corresponding to two diet variants that used to feed Nile tilapia for 20 successive days: a basal (control), and P. boergesenii water extract supplemented group. Fish samples were collected at 10-days intervals throughout the experiment. Serum biochemical constituents, total antioxidant capacity (TAC), and some immune related genes expression of the spleen and intestinal tissues of experimental fish were studied, as well as histological examination of fish immune tissues. Moreover, following 20 days of feeding, the susceptibility of Nile tilapia to P. putida infection was evaluated to assess the protective effect of the used extract. The findings indicated that the studied parameters were significantly increased, and the best immune response profiles were observed in fish fed P. boergesenii water extract for 20 successive days. A bacterial challenge experiment using P. putida resulted in higher survival within the supplemented fish group than the control. Thus, the lowered post-challenge mortality of the fish may be related to the protection provided by the stimulation of the innate immune system, reduced oxidative stress by higher activity of TAC, and elevated levels of expression of iterleukin-1beta (IL-1ß), beta-defensin (ß-defensin), and natural killer-lysin (NKl). Moreover, the constituents of the extract used showed potential protective activity for histological features of the supplemented fish group when compared to the control. Collectively, this study presents a great insight on the protective role of P. boergesenii water extract as an additive in Nile tilapia feed which suggests its potential for improving the immune response against P. putida infection.

Effect of balloon dilatation among adult population with eustachian tube dysfunction: a systematic review.

PURPOSE: This study aimed to assess the efficacy and safety of ballon dilation of the eustachian tube (BDET) in adult population suffering from Eustachian tube dysfunction (ETD). METHODS: Following PRISMA criteria, a systematic review was conducted by searching PubMed, Cochrane, and Embase databases from January 2015 to March 2024. The primary outcomes included Eustachian Tube Score (ETS), tympanometry, and Valsalva maneuver. The quality of studies was assessed using the Quality in Prognostic Studies (QUIPS) instrument. RESULTS: Overall, 11 studies were incorporated into the systematic review: two RCTs, three prospective investigations, and six retrospective studies. The balloon dilation in all investigations was performed using either Spiggle & Theis or Acclarent catheters for balloon dilation. There was heterogeneity across studies examining the effect of BDET on persistent ETD in terms of patient selection, period of follow-up, administration of conservative or surgical therapies, and use of assessment methods. Overall, the treatment yielded alleviation of symptoms, which either exhibited stability over time or demonstrated further improvement after an average duration of follow-up. Moreover, the incidence of complications was categorized as low and resolving spontaneously. The majority of the studies exhibited a high risk of bias related to confounding variables, and consequently, the overall risk of bias across most studies was considered high. CONCLUSION: The findings suggest BDET holds promise for ETD treatment, reducing symptom severity with minimal complications. Nonetheless, there is a need for improved studies that adhere to established indications, methodologies, and outcomes to establish a more robust body of evidence.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Nanoscopic Characterization of Cell Migration under Flow Using Optical and Electron Microscopy.

Hematopoietic stem/progenitor cell (HSPC) and leukemic cell homing is an important biological phenomenon that takes place through essential interactions with adhesion molecules on an endothelial cell layer. The homing process of HSPCs begins with the tethering and rolling of the cells on the endothelial layer, which is achieved by the interaction between selectins on the endothelium to the ligands on HSPC/leukemic cells under shear stress of the blood flow. Although many studies have been based on in vitro conditions of the cells rolling over recombinant proteins, significant challenges remain when imaging HSPC/leukemic cells on the endothelium, a necessity when considering characterizing cell-to-cell interaction and rolling dynamics during cell migration. Here, we report a new methodology that enables imaging of stem-cell-intrinsic spatiotemporal details during its migration on an endothelium-like cell monolayer. We developed optimized protocols that preserve transiently appearing structures on HSPCs/leukemic cells during its rolling under shear stress for fluorescence and scanning electron microscopy characterization. Our new experimental platform is closer to in vivo conditions and will contribute to indepth understanding of stem-cell behavior during its migration and cell-to-cell interaction during the process of homing.

Mouth rinses efficacy on salivary SARS-CoV-2 viral load: A randomized clinical trial.

Considering the global trend to confine the COVID-19 pandemic by applying various preventive health measures, preprocedural mouth rinsing has been proposed to mitigate the transmission risk of SARS-CoV-2 in dental clinics. The study aimed to investigate the effect of different mouth rinses on salivary viral load in COVID-19 patients. This study was a single-center, randomized, double-blind, six-parallel-group, placebo-controlled clinical trial that investigated the effect of four mouth rinses (1% povidone-iodine, 1.5% hydrogen peroxide, 0.075% cetylpyridinium chloride, and 80 ppm hypochlorous acid) on salivary SARS-CoV-2 viral load relative to the distilled water and no-rinse control groups. The viral load was measured by quantitative reverse transcription PCR (RT-qPCR) at baseline and 5, 30, and 60 min post rinsing. The viral load pattern within each mouth rinse group showed a reduction overtime; however, this reduction was only statistically significant in the hydrogen peroxide group. Further, a significant reduction in the viral load was observed between povidone-iodine, hydrogen peroxide, and cetylpyridinium chloride compared to the no-rinse group at 60 min, indicating their late antiviral potential. Interestingly, a similar statistically significant reduction was also observed in the distilled water control group compared to the no-rinse group at 60 min, proposing mechanical washing of the viral particles through the rinsing procedure. Therefore, results suggest using preprocedural mouth rinses, particularly hydrogen peroxide, as a risk-mitigation step before dental procedures, along with strict adherence to other infection control measures.

Hepatitis delta virus infection prevalence, diagnosis and treatment in the Middle East: A scoping review.

Hepatitis D virus (HDV) infection is a global public health concern, especially because of its unique existence in the presence of hepatitis B virus infection. HDV infection is estimated to affect 12 million people globally. Having a clearer understanding of its prevalence in all regions of the world is essential for helping direct preventive and early interventional treatment. This mini-review assessed the literature over the last 10 years to determine the prevalence, diagnostic means and treatment guidelines available for HDV in the Middle East. The search found limited data available in 21 articles, of which 18 were studies focused on Iran. Prevalence rates ranged dramatically among the countries, and none of the 12 countries included in the search had specific HDV guidelines. This review highlights the urgent need for more precise data for the Middle East region to help establish early diagnosis and treatment options for HDV.

Neuroprotective efficacy of the bacterial metabolite, prodigiosin, against aluminium chloride-induced neurochemical alternations associated with Alzheimer's disease murine model: Involvement of Nrf2/HO-1/NF-κB signaling.

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+ /K+ -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.

Efficacy of prophylactic pre-operative desmopressin administration during functional endoscopic sinus surgery for chronic rhinosinusitis: A systematic review and meta-analysis of randomised placebo-controlled trials.

OBJECTIVES: To examine the efficacy of prophylactic desmopressin versus placebo among patients undergoing functional endoscopic sinus surgery (FESS). DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). SETTING: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Scopus, and Web of Science databases were screened from inception until 18 March 2022. PARTICIPANTS: Patients undergoing FESS. MAIN OUTCOME MEASURES: Primary efficacy endpoints comprised intraoperative blood loss, visual clarity, and operation time. Secondary endpoints comprised side effects. The efficacy endpoints were summarised as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). RESULTS: Five RCTs comprising 380 patients (desmopressin = 191 patients and placebo = 189 patients) were included. Collectively, the included RCTs had an overall low risk of bias. The pooled results showed that the mean intraoperative blood loss (n = 5 RCTs, MD = -37.97 ml, 95% CI [-56.97, -18.96], p < .001), 5-point Boezaart scores (n = 2 RCTs, MD = -.97, 95% CI [-1.21, -.74], p < .001), and 10-point Boezaart scores (n = 2 RCTs, MD = -3.00, 95% CI [-3.61, -2.40], p < .001) were significantly reduced in favour of the desmopressin group compared with the placebo group. Operation time did not significantly differ between both groups (n = 5 RCTs, MD = -3.73 min, 95% CI [-14.65, 7.18], p = .50). No patient in both groups developed symptomatic hyponatremia (n = 3 RCTs, 194 patients) or thromboembolic events (n = 2 RCTs, 150 patients). CONCLUSIONS: Among patients undergoing FESS, prophylactic administration of desmopressin does not correlate with significant clinical benefits. Data on safety is limited. Future research may explore the synergistic antihaemorrhagic efficacy and safety of tranexamic acid (TXA) plus desmopressin versus TXA alone among patients undergoing FESS.

Advancement of management information system for discovering fraud in master card based intelligent supervised machine learning and deep learning during SARS-CoV2.

During coronavirus (SARS-CoV2) the number of fraudulent transactions is expanding at a rate of alarming (7,352,421 online transaction records). Additionally, the Master Card (MC) usage is increasing. To avoid massive losses, companies of finance must constantly improve their management information systems for discovering fraud in MC. In this paper, an approach of advancement management information system for discovering of MC fraud was developed using sequential modeling of data depend on intelligent forecasting methods such as deep Learning and intelligent supervised machine learning (ISML). The Long Short-Term Memory Network (LSTM), Logistic Regression (LR), and Random Forest (RF) were used. The dataset is separated into two parts: the training and testing data, with a ratio of 8:2. Also, the advancement of management information system has been evaluated using 10-fold cross validation depend on recall, f1-score, precision, Mean Absolute Error (MAE), Receiver Operating Curve (ROC), and Root Mean Square Error (RMSE). Finally various techniques of resampling used to forecast if a transaction of MC is genuine/fraudulent. Performance for without re-sampling, with under-sampling, and with over-sampling is measured for each Algorithm. Highest performance of without re-sampling was 0.829 for RF algorithm-F score. While for under-sampling, it was 0.871 for LSTM algorithm-RMSE. Further, for over-sampling, it was 0.921 for both RF algorithm-Precision and LSTM algorithm-F score. The results from running advancement of management information system revealed that using resampling technique with deep learning LSTM generated the best results than intelligent supervised machine learning.

An evaluation of neuropsychiatric manifestations in systemic lupus erythematosus patients in Saudi Arabia and their associated factors.

OBJECTIVES: To establish the prevalence of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) symptoms in Saudi Arabia and the variables that are linked to it. METHODS: This cross-sectional study was conducted in June 2021 among SLE patients in Saudi Arabia. The Saudi Rheumatism Association exploited social media platforms to provide a self-administered online questionnaire to SLE patients. All data analyses were performed using the Statistical Packages for Social Sciences (SPSS) version 26. RESULTS: Two hundred and eight SLE patients participated in the study (females 91.3% vs. males 8.7%). In addition, 13.5% of patients had a family history of SLE, and 26% had SLE for one to 3 years. The most common symptoms of NPSLE were alteration or loss of sensation (53.4%), followed by fear (52.4%), and headache (48.1%). The prevalence of patients with NPSLE was 40%. In a multivariate regression model, fear, altered sensations, cerebrovascular illness, sleep disruption, and diminished interest in routine activities were identified as independent risk variables for NPSLE CONCLUSION: Nearly half of SLE patients demonstrated NP manifestations, with significant symptoms including fear, alteration of sensation, cerebrovascular disease, sleep disturbance, and reduced interest in normal activities. To detect the pathophysiology of NPSLE, it is necessary to understand the relationship between neuropsychiatric morbidity and other relevant rheumatic disorders in the SLE population.

ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis.

ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity. Knockdown of either ADAMTS-1 or syndecan-4 increased cellular responses to vascular endothelial growth factor A isoform VEGFA164, and increased ex vivo aortic ring microvessel sprouting. On fibronectin, knockdown of either protein enhanced migration and promoted formation of long α5 integrin-containing fibrillar adhesions. However, integrin α5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naïve endothelial cells on cell-conditioned matrix from ADAMTS-1 and syndecan-4 knockdown cells demonstrated that the altered adhesive behaviour was matrix dependent, and this correlated with a lack of expression of fibulin-1: an extracellular matrix co-factor for ADAMTS-1 that is known to inhibit migration. These findings support the notion that ADAMTS-1 and syndecan-4 are functionally interconnected in regulating cell migration and angiogenesis, via collaboration with MMP9 and fibulin-1.This article has an associated First Person interview with the first author of the paper.

Successful heart transplantation from a donor with bacterial and fungal bloodstream infection: Case report of donor optimization strategy.

Donor optimization is vital to increase donor hearts utilized for transplantation. We report a case of a 34-year-old female with end-stage cardiomyopathy that was admitted to the intensive care unit on inotropic support with progressive decline (INTERMACS-2). She was offered a donor heart from a 14-year male that was found to have Klebsiella pneumoniae bacteremia and candidemia co-infection. The donor was transferred to our hospital and optimized hemodynamically and biochemically. Targeted antimicrobial and antifungal therapy based on the susceptibility testing was established in the donor till blood cultures were negative. The recipient received similar prophylactic therapy for 2-week course starting 24-h before transplantation. The patient was transplanted with no clinical consequences. She was discharged home in 4 weeks post-transplantation. Her 3-month follow-up was completely uneventful.

The Relationship between Cannabis and Tobacco Co-administration and Long-Term Patterns of Cannabis Use in Young Adults Who Use Stimulants: A Prospective Population-Based Study.

BACKGROUND: Co-administering cannabis with tobacco (i.e. co-administration of the substances mixed together) is a common practice among cannabis users, but the consequences of this practice are not well understood. This study examines the relationship between co-administering cannabis with tobacco and the long-term frequency of cannabis use in a young adult population group with high rates of cannabis and tobacco use. METHODS: The data are from an Australian prospective population-based study of young adults who recurrently used amphetamine-type stimulants (ATS). The mean age of participants was 20.8 years at baseline, sample size (n = 277), and 47% were female. We examined the frequency and quantity of cannabis consumption over 4 ½ years. Negative binomial regression analysis was conducted to examine the frequency of cannabis use at 12-month follow-up and at 4 ½ years, with co-administering practices as the predictor. RESULTS: At every time interval, participants who always co-administered their cannabis with tobacco used cannabis on more days in the last month than those who only sometimes co-administered, rarely co-administered, or never co-administered these substances (p < 0.001). Sometimes co-administering cannabis with tobacco at baseline predicted more frequent cannabis use at 12-month follow-up (adjusted IRR: 2.25, 95% CI: 1.05, 4.78), independently of the baseline frequency of cannabis use. However, levels of co-administering cannabis with tobacco at 12-month follow-up (rarely, sometimes, and always) did not predict high levels of cannabis use at 4 ½ years follow-up after adjusting for cannabis use at 12-month follow-up. CONCLUSIONS: Among people who use ATS and cannabis, frequent cannabis use may be a marker of the practice of co-administering cannabis with tobacco, and can be used to target tobacco cessation interventions in these populations.

Do Saudi medical schools consider the core topics in undergraduate medical curricula?

BACKGROUND: Most of the medical schools in Saudi Arabia are currently evolving their curricula in accordance with the most recognized medical education trends worldwide. Undergraduate medical school's curriculum should be compatible with community health needs. Therefore, the study aims to explore the current contents of Saudi undergraduate medical curricula and to check if the core topics that were internationally recognized were implemented in their curriculum. METHODOLOGY: An online questionnaire was designed and sent to 37 deans of medical schools in Saudi Arabia. The deans or the vice-deans in charge of the curriculum were asked to complete the pre-designed questionnaire, which assessed the status of inclusion of the core topics in the curriculum of their affiliated schools. Each listed core topic was evaluated according to five options for each subject: not included, separate required course, part of the required course, separate elective course, and part of an elective course. RESULTS: Twenty four out of 37 (65%) Saudi medical schools completed the survey questionnaire. Almost all core topics, such as communication skills, evidence-based medicine, patient safety, professionalism were included in the curricula of Saudi medical schools as separate required courses or as part of required courses or elective courses. Complementary and alternative medicine and the history of medicine were the topics least taught in Saudi medical colleges, as 25% of the schools did not include them in their curricula. CONCLUSION: The majority (65%) of the internationally recognized core topics were included in the Saudi undergraduate medical curricula. Evidence-based medicine, complementary medicine, the Saudi healthcare system, patient safety, and professionalism/medical ethics should be part of compulsory credited courses in all Saudi undergraduate medical curricula.

Blockchain Empowered Federated Learning Ecosystem for Securing Consumer IoT Features Analysis.

Resource constraint Consumer Internet of Things (CIoT) is controlled through gateway devices (e.g., smartphones, computers, etc.) that are connected to Mobile Edge Computing (MEC) servers or cloud regulated by a third party. Recently Machine Learning (ML) has been widely used in automation, consumer behavior analysis, device quality upgradation, etc. Typical ML predicts by analyzing customers' raw data in a centralized system which raises the security and privacy issues such as data leakage, privacy violation, single point of failure, etc. To overcome the problems, Federated Learning (FL) developed an initial solution to ensure services without sharing personal data. In FL, a centralized aggregator collaborates and makes an average for a global model used for the next round of training. However, the centralized aggregator raised the same issues, such as a single point of control leaking the updated model and interrupting the entire process. Additionally, research claims data can be retrieved from model parameters. Beyond that, since the Gateway (GW) device has full access to the raw data, it can also threaten the entire ecosystem. This research contributes a blockchain-controlled, edge intelligence federated learning framework for a distributed learning platform for CIoT. The federated learning platform allows collaborative learning with users' shared data, and the blockchain network replaces the centralized aggregator and ensures secure participation of gateway devices in the ecosystem. Furthermore, blockchain is trustless, immutable, and anonymous, encouraging CIoT end users to participate. We evaluated the framework and federated learning outcomes using the well-known Stanford Cars dataset. Experimental results prove the effectiveness of the proposed framework.

Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.

Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthetic and natural chemicals are effective for cancer chemoprevention, i.e., the use of exogenous medicine to inhibit or impede tumor development. They help regulate molecular pathways linked to the development and spread of cancer. They can enhance antioxidant status, inactivating carcinogens, suppressing proliferation, inducing cell cycle arrest and death, and regulating the immune system. While focusing on four main categories of plant-based anticancer agents, i.e., epipodophyllotoxin, camptothecin derivatives, taxane diterpenoids, and vinca alkaloids and their mode of action, we review the anticancer effects of phytochemicals, like quercetin, curcumin, piperine, epigallocatechin gallate (EGCG), and gingerol. We examine the different signaling pathways associated with cancer and how inflammation as a key mechanism is linked to cancer growth.

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses.

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine-glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine-glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.