The lincRNA JUNI regulates the stress-dependent induction of c-Jun, cellular migration and survival through the modulation of the DUSP14-JNK axis.

Cancer cells employ adaptive mechanisms to survive various stressors, including genotoxic drugs. Understanding the factors promoting survival is crucial for developing effective treatments. In this study, we unveil a previously unexplored long non-coding RNA, JUNI (JUN-DT, LINC01135), which is upregulated by genotoxic drugs through the activation of stress-activated MAPKs, JNK, and p38 and consequently exerts positive control over the expression of its adjacent gene product c-Jun, a well-known oncoprotein, which transduces signals to multiple transcriptional outputs. JUNI regulates cellular migration and has a crucial role in conferring cellular resistance to chemotherapeutic drugs or UV radiation. Depletion of JUNI markedly increases the sensitivity of cultured cells and spheroids to chemotherapeutic agents. We identified 57 proteins interacting with JUNI. The activity of one of them the MAPK phosphatase and inhibitor, DUSP14, is counteracted by JUNI, thereby, facilitating efficient JNK phosphorylation and c-Jun induction when cells are exposed to UV radiation. The antagonistic interplay with DUSP14 contributes not only to c-Jun induction but also augments the survival of UV-exposed cells. In summary, we introduce JUNI as a novel stress-inducible regulator of c-Jun, positioning it as a potential target for enhancing the sensitivity of cancer cells to chemotherapy.

A Comprehensive Review on Nanoparticles as Drug Delivery System and Their Role for Management of Hypertension.

The current global epidemic of hypertension is not a disease in and of itself but rather a significant risk factor for serious cardiovascular conditions such as peripheral artery disease, heart failure, myocardial infarction, and stroke. Although many medications that work through various mechanisms of action are available on the market in conventional formulations to treat hypertension, these medications face significant difficulties with their bioavailability, dosing, and associated side effects, which significantly reduces the effectiveness of their therapeutic interventions. Numerous studies have shown that nanocarriers and nanoformulations can minimize the toxicity associated with high doses of the drug while greatly increasing the drug's bioavailability and reducing the frequency of dosing.

This review sheds light on the difficulties posed by traditional antihypertensive formulations and highlights the necessity of oral nanoparticulate systems to solve these issues. Because hypertension has a circadian blood pressure pattern, chronotherapeutics can be very important in treating the condition. On the other hand, nanoparticulate systems can be very important in managing hypertension.

Antioxidant Defense and Ionic Homeostasis Govern Stage-Specific Response of Salinity Stress in Contrasting Rice Varieties.

Salt stress is one of the most severe environmental stresses limiting the productivity of crops, including rice. However, there is a lack of information on how salt-stress sensitivity varies across different developmental stages in rice. In view of this, a comparative evaluation of contrasting rice varieties CSR36 (salt tolerant) and Jaya (salt sensitive) was conducted, wherein NaCl stress (50 mM) was independently given either at seedling (S-stage), tillering (T-stage), flowering (F-stage), seed-setting (SS-stage) or throughout plant growth, from seedling till maturity. Except for S-stage, CSR36 exhibited improved NaCl stress tolerance than Jaya, at all other tested stages. Principal component analysis (PCA) revealed that the improved NaCl stress tolerance in CSR36 coincided with enhanced activities/levels of enzymatic/non-enzymatic antioxidants (root ascorbate peroxidase for T- (2.74-fold) and S+T- (2.12-fold) stages and root catalase for F- (5.22-fold), S+T- (2.10-fold) and S+T+F- (2.61-fold) stages) and higher accumulation of osmolytes (shoot proline for F-stage (5.82-fold) and S+T+F- (2.31-fold) stage), indicating better antioxidant capacitance and osmotic adjustment, respectively. In contrast, higher shoot accumulation of Na+ (14.25-fold) and consequent increase in Na+/K+ (14.56-fold), Na+/Mg+2 (13.09-fold) and Na+/Ca+2 (8.38-fold) ratio in shoot, were identified as major variables associated with S-stage salinity in Jaya. Higher root Na+ and their associated ratio were major deriving force for other stage specific and combined stage salinity in Jaya. In addition, CSR36 exhibited higher levels of Fe3+, Mn2+ and Co3+ and lower Cl- and SO42-, suggesting its potential to discriminate essential and non-essential nutrients, which might contribute to NaCl stress tolerance. Taken together, the findings provided the framework for stage-specific salinity responses in rice, which will facilitate crop-improvement programs for specific ecological niches, including coastal regions.

Polymeric Microfluidic Fuel Cells with Controlled Printed Patterns.

Since its first appearance almost a couple of decades ago, microfluidic fuel cells (MFFCs) have gained considerable research momentum due to their potential applications in portable devices. The main focus has been on the effective fabrication of microfluidic channels with different materials, where the manufacturing limitations proved to be the main stumbling blocks. Paper-based MFFCs have been reported with some success, where the porosity of the flow channel medium drives the reactants, greatly reducing the need for elaborate external devices and complex manufacturing obstacles, although the longevity of these cells remains questionable. The current article addresses this issue by replacing the paper-based flow channels with 3D-printed substrates of different structural forms to serve as pathways for controlled flow and mixing responses of the reactant liquids without the use of other devices, such as micro pumps and valves. The line-by-line material consolidation mechanics of fused filament fabrication and the porous mesostructural responses of a commercial polymer filament are combined to build the microfluidic fuel channels of varying configurations. Numerical and experimental characterizations proved the cells to perform better than the current paper-based counterparts, apart from better longevity and possible new opportunities for future improvements based on more complex micro-, meso-, and macrostructural advances.

A Case of Non-cirrhotic Portal Hypertension With Antiphospholipid Syndrome.

Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV) are two causes of non-cirrhotic portal hypertension (NCPH), which is a vascular liver disease wherein clinical signs of portal hypertension (PHT), such as esophageal varices, ascites, and splenomegaly develop in the absence of cirrhosis and portal vein thrombosis. The etiology often remains unidentified, but herein we present the case of a 56-year-old male with NCPH and refractory ascites who underwent liver biopsy confirming NRH and OPV. Etiological workup revealed beta-2 glycoprotein-1 and anticardiolipin antibodies, concerning antiphospholipid syndrome (APS) despite no prior history of thrombosis. The patient underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure for his refractory ascites and was started on prophylactic anticoagulation owing to a concern for APS with clinical improvement in his ascites and shortness of breath. Pursuing TIPS earlier in the setting of refractory ascites, as well as offering anticoagulation therapy for patients with possible APS to prevent the development of potential thromboses, could be appropriate recommendations to prevent complications in the disease course. This case report highlights the need for further investigations on the etiologies, diagnosis pathways, and treatment options for NCPH.

An automatic glucose monitoring system based on periplasmic binding proteins for online bioprocess monitoring.

Glucose is one of the most vital nutrients in all living organisms, so its monitoring is critical in healthcare and bioprocessing. Enzymatic sensors are more popular as a technology solution to meet the requirement. However, periplasmic binding proteins have been investigated extensively for their high sensitivity, enabling microdialysis sampling to replace existing complex and expensive glucose monitoring solutions based on enzymatic sensors. The binding proteins are used as optical biosensors by introducing an environment-sensitive fluorophore to the protein. The biosensor's construction, characterization, and potential application are well studied, but a complete glucose monitoring system based on it is yet to be reported. This work documents the development of the first glucose sensor prototype based on glucose binding protein (GBP) for automatic and continuous glucose measurements. The development includes immobilizing the protein into reusable chips and a low-cost solution for non-invasive glucose sampling in bioprocesses using microdialysis sampling technique. A program was written in LabVIEW to accompany the prototype for the complete automation of measurement. The sampling technique allowed glucose measurements of a few micromolar to 260 mM glucose levels. A thorough analysis of the sampling mode and the device's performance was conducted. The reported measurement accuracy was 81.78%, with an RSD of 1.83%. The prototype was also used in online glucose monitoring of E. coli cell culture. The mode of glucose sensing can be expanded to the measurement of other analytes by switching the binding proteins.

Programmed Death-1 Inhibitor Immunotherapy-Induced Symptomatic Toxic Thyroid Nodule.

Immune checkpoint inhibitors, specifically programmed death-ligand 1 (PD-LI) inhibitors, are immune modifying medications that increasingly treat specific types of cancer. They are known to cause many side effects, including thyroid-related side effects. The use of PD-L1 inhibitors can cause hypothyroidism most commonly, while hyperthyroidism occurs less frequently. This case report describes a patient who developed a toxic thyroid nodule while taking the PD-L1 inhibitor, avelumab, for the treatment of Merkel cell carcinoma. It highlights the need for more research into the specific mechanisms by which these therapies can cause hyperthyroidism. It also raises the question regarding the association between the use of these medications and the development or worsening of thyroid nodules.

Deciphering the impact of endoparasitic infection on immune response and gut microbial composition of Channa punctata.

Intestinal parasitic infections caused by helminths are globally distributed and are a major cause of morbidity worldwide. Parasites may modulate the virulence, gut microbiota diversity and host responses during infection. Despite numerous works, little is known about the complex interaction between parasites and the gut microbiota. In the present study, the complex interplay between parasites and the gut microbiota was investigated. A total of 12 bacterial strains across four major families, including Enterobacteriaceae, Morganellaceae, Flavobacteriaceae, and Pseudomonadaceae, were isolated from Channa punctata, infected with the nematode species Aporcella sp., Axonchium sp., Tylencholaimus mirabilis, and Dioctophyme renale. The findings revealed that nematode infection shaped the fish gut bacterial microbiota and significantly affected their virulence levels. Nematode-infected fish bacterial isolates are more likely to be pathogenic, with elevated hemolytic activity and biofilm formation, causing high fish mortality. In contrast, isolates recovered further from non-parasitised C. punctata were observed to be non-pathogenic and had negligible hemolytic activity and biofilm formation. Antibiogram analysis of the bacterial isolates revealed a disproportionately high percentage of bacteria that were either marginally or multidrug resistant, suggesting that parasitic infection-induced stress modulates the gut microenvironment and enables colonization by antibiotic-resistant strains. This isolation-based study provides an avenue to unravel the influence of parasitic infection on gut bacterial characteristics, which is valuable for understanding the infection mechanism and designing further studies aimed at optimizing treatment strategies. In addition, the cultured isolates can supplement future gut microbiome studies by providing wet lab specimens to compare (meta)genomic information discovered within the gut microenvironment of fish.

Role of gut microbiota in cardiovascular diseases - a comprehensive review.

The connection between cardiovascular illnesses and the gut microbiota has drawn more and more attention in recent years. According to research, there are intricate relationships between dietary elements, gut bacteria, and their metabolites that affect cardiovascular health. In this study, the role of gut microbiota in cardiovascular disorders is examined, with an emphasis on the cardiac consequences brought on by changes in gut microbiota. This essay discusses the gut-heart axis in depth and in detail. It talks about clinical research looking at how soy consumption, probiotic supplements, and dietary changes affected gut microbiota and cardiovascular risk variables. Our goal is to clarify the possible pathways that connect gut microbiota to cardiovascular health and the implications for upcoming treatment approaches. The authors examine the composition, roles, and effects of the gut microbiota on cardiovascular health, including their contributions to hypertension, atherosclerosis, lipid metabolism, and heart failure. Endotoxemia, inflammation, immunological dysfunction, and host lipid metabolism are some of the potential processes investigated for how the gut microbiota affects cardiac outcomes. The research emphasizes the need for larger interventional studies and personalized medicine strategies to completely understand the complexity of the gut-heart axis and its implications for the management of cardiovascular disease. The development of novel treatment strategies and cutting-edge diagnostic technologies in cardiovascular medicine may be facilitated by a better understanding of this axis.

Impact of artificial intelligence on the diagnosis, treatment and prognosis of endometrial cancer.

Endometrial cancer is one of the most prevalent tumours in females and holds an 83% survival rate within 5 years of diagnosis. Hypoestrogenism is a major risk factor for the development of endometrial carcinoma (EC) therefore two major types are derived, type 1 being oestrogen-dependent and type 2 being oestrogen independent. Surgery, chemotherapeutic drugs, and radiation therapy are only a few of the treatment options for EC. Treatment of gynaecologic malignancies greatly depends on diagnosis or prognostic prediction. Diagnostic imaging data and clinical course prediction are the two core pillars of artificial intelligence (AI) applications. One of the most popular imaging techniques for spotting preoperative endometrial cancer is MRI, although this technique can only produce qualitative data. When used to classify patients, AI improves the effectiveness of visual feature extraction. In general, AI has the potential to enhance the precision and effectiveness of endometrial cancer diagnosis and therapy. This review aims to highlight the current status of applications of AI in endometrial cancer and provide a comprehensive understanding of how recent advancements in AI have assisted clinicians in making better diagnosis and improving prognosis of endometrial cancer. Still, additional study is required to comprehend its strengths and limits fully.

Personalized Approach to Chronic Antibiotic-Refractory Pouchitis: A Case Report and Review of the Literature.

Patients who undergo restorative proctocolectomy and ileoanal anastomosis can develop pouchitis as a common chronic complication. A rare subset of patients fails to respond to multiple antibiotic therapies and develop chronic antibiotic-refractory pouchitis (CARP). We present a case of a 45-year-old male with pouchitis refractory to chronic antibiotic therapy and histology demonstrating chronic inflammatory changes. Management involved mesalamine and probiotics, resulting in a positive clinical response and symptom absence on follow-up. This case highlights the intricacies of treating chronic pouchitis post ileoanal anastomosis, showcasing the efficacy of a personalized approach using mesalamine and probiotics. CARP is emerging as an entity associated with poor quality of life and increased healthcare costs. CARP fails to respond to multiple courses of antibiotic therapy. Therefore, the management of CARP is difficult and limited. Current literature on the management of CARP is scarce and mainly involves immunomodulatory therapy and probiotics. It is essential to keep this differential diagnosis in mind in patients with recurrent pouchitis episodes and start them on immunomodulator treatment and probiotics rather than repeated courses of antibiotics.

Paroxysmal atrial fibrillation and hemochromatosis: a narrative review.

Paroxysmal atrial fibrillation (PAF) and hemochromatosis have a complex relationship. This review explores its mechanisms, prevalence, correlations, and clinical manifestations. Hereditary hemochromatosis (HH) involves iron overload due to HFE protein mutations, while atrial fibrillation (AF) is characterized by irregular heart rhythms. Iron overload in hemochromatosis can promote cardiac arrhythmias. AF is prevalent in developed countries and may be linked to cryptogenic strokes. Genetic variations and demographic factors influence the occurrence of both conditions. HH affects multiple organ systems, including the heart, while AF causes palpitations and reduced exercise tolerance. Diagnosis involves iron markers, genotypic testing, and electrocardiogram (ECG) findings. Treatment strategies focus on reducing iron levels in hemochromatosis and managing AF through antithrombotic therapy and rhythm control. Untreated hemochromatosis carries a higher risk of complications, and PAF is associated with increased cardiovascular-related mortality. For better understanding of the mechanisms and to improve management, additional studies are required. Tailored approaches and combined treatments may enhance patient outcomes.

A review of non-invasive samples and tools in kala-azar diagnosis and test of cure.

The recurrence of visceral leishmaniasis (VL), also called kala-azar (KA), in endemic regions of tropical countries like India, is primarily attributed to asymptomatic VL, post-kala azar dermal leishmaniasis (PKDL), and human immunodeficiency virus (HIV) co-infection. To effectively manage VL cases and elimination targets, an early and rapid diagnosis as well as accurate field surveillance is highly essential. The traditional sampling methods like bone marrow (BM), spleen, and lymph node (LN) tissue aspirations are invasive, painful, tedious, and prone to nosocomial infections, require skilled persons and hospital facilities, and are not feasible in rural areas. Therefore, there is an urgent requirement for the adoption of a patient-friendly, non-invasive, non-hospitalized sampling procedure that ensures an effective VL diagnosis. This review aims to meticulously evaluate the most recent scientific research that focuses on the precision, feasibility, and applicability of non-invasive sampling (NIS) and techniques for the diagnosis and test of cure of VL, particularly in resource-limited settings. Apart from that, the non-invasive techniques (NIT) that have shown promising results while monitoring VL treatment response and relapse are also reviewed. The limitations associated with NIT and possible improvements in this regard are discussed as well to improve the diagnosis and management of VL.

Nanocomposite Marvels: Unveiling Breakthroughs in Photocatalytic Water Splitting for Enhanced Hydrogen Evolution.

An overview of the significant innovations in photocatalysts for H2 development, photocatalyst selection criteria, and photocatalytic modifications to improve the photocatalytic activity was examined in this Review, as well as mechanisms and thermodynamics. A variety of semiconductors have been examined in a structured fashion, such as TiO2-, g-C3N4-, graphene-, sulfide-, oxide-, nitride-, oxysulfide-, oxynitrides, and cocatalyst-based photocatalysts. The techniques for enhancing the compatibility of metals and nonmetals is discussed in order to boost photoactivity within visible light irradiation. In particular, further deliberation has been carried out on the development of heterojunctions, such as type I, type II, and type III, along with Z-systems, and S-scheme systems. It is important to thoroughly investigate these issues in the sense of visible light irradiations to enhance the efficacy of photocatalytic action. In fact, another advancement in this area may include hiring mediators including grapheme oxide and metals to establish indirect Z-scheme montages with a correct band adjustment. The potential consideration of reaction chemology, mass transfer, kinetics of reactions, restriction of light diffusion, and the process and selection of suitable light and photoreactor also will optimize sustainable hydrogen output efficiency and selectivity.

Antibiotic susceptibility patterns of pathogens isolated from hospitalized patients with advanced HIV disease (AHD) in Bihar, India.

Objectives: To describe the prevalence of common bacterial pathogens and antibiotic susceptibility patterns amongst advanced HIV disease (AHD) patients admitted between May 2019 and March 2021 to a Médecins Sans Frontières (MSF)-supported AHD inpatient unit in Bihar, India. Methods: A retrospective analysis of routinely collected demographic, clinical and microbiological data. Antibacterial susceptibility testing was done by an accredited referral laboratory using the modified Kirby-Bauer disc diffusion method. Results: A total of 238 isolates from 577 patients were identified through culture testing. Patient median (IQR) age was 38 (31-45) years, and 75% were male. Predominant sample types included blood (600; 38%), urine (266; 17%) and sputum (178; 11%). Of the isolated bacteria, Escherichia coli (80; 13.9%) was the most prevalent, followed by Klebsiella pneumonia (54; 9.4%), Pseudomonas aeruginosa (22; 3.8%), Klebsiella oxytoca (10; 1.7%), Proteus mirabilis (9; 1.6%), and Acinetobacter baumannii (7; 1.2%). The resistance pattern showed that most bacterial isolates were highly resistant to commonly prescribed antibiotics such as third-generation cephalosporins, fluoroquinolones and co-trimoxazole. Most pathogens were moderately resistant to antibiotics from the WHO Watch group, such as meropenem and piperacillin/tazobactam. In contrast, isolates were more susceptible to aminoglycosides, such as amikacin, gentamicin and nitrofurantoin. Conclusions: In Bihar, inpatients with AHD displayed a concerning array of antibiotic-resistant infections. This study provides a starting point from which further work on antimicrobial resistance in this vulnerable cohort of patients can be conducted.

Morin hydrate ameliorates heat-induced testicular impairment in a mouse model.

BACKGROUND: Heat stress is known to adversely affect testicular activity and manifest the pathogenesis of spermatogenesis. Morin hydrate is a plant-derived compound, which contains a wide range of biological activities. Thus, it is hypothesized that morin hydrate might have an ameliorative effect on heat-induced testicular impairment. There has not been any research on the impact of morin hydrate on heat-induced testicular damage. METHODS: The experimental mice were divided into four groups, groups1 as the normal control group (CN), and the second which underwent heat stress (HS) by immersing the lower body for 15 min in a thermostatically controlled water bath kept at 43 °C (HS), and third and fourth heat-stressed followed by two different dosages of morin hydrate 10 mg/kg (HSM10) and 100 mg/kg (HSM100) for 14 days. RESULTS: Morin hydrate treatment at 10 mg/kg improved, circulating testosterone levels (increases 3ßHSD), and oxidative stress along with improvement in the testis and caput and corpus epididymis histoarchitecture, however, both doses of morin hydrate improved sperm parameters. Morin hydrate treatment significantly increases germ cell proliferation, (GCNA, BrdU staining), expression of Bcl2 and decreases expression of active caspase 3. Heat stress also decreased the expression of AR, ER- α, and ER-ß, and Morin hydrate treatment increased the expression of these markers in the 10 mg/kg treatment group. CONCLUSION: Morin hydrate ameliorates heat-induced testicular impairment modulating testosterone synthesis, germ cell proliferation, and oxidative stress. These effects could be manifested by regulating androgen and estrogen receptors. However, the two doses showed differential effects of some parameters, which requires further investigations.

Role of microRNA in colorectal carcinoma (CRC): a narrative review.

MicroRNAs (miRNAs) are short non-coding RNAs that play a critical role in regulating gene expression by binding to target messenger RNAs (mRNAs). They were first discovered around 8 years after the identification of the first miRNA in 1993, and since then, there has been a significant increase in miRNA-related research and discoveries. MiRNAs have been implicated in various biological processes, including cancer, particularly in colorectal cancer (CRC). In CRC, miRNAs act as either oncogenes or tumor suppressors, influencing essential cellular functions such as cell proliferation, apoptosis, angiogenesis, and metastasis. The dysregulation of miRNAs in CRC can arise from different factors, leading to abnormal expression levels of their target mRNAs and subsequently affecting protein production. Consequently, miRNAs may directly target oncogenes or tumor suppressor genes, thereby contributing to cancer initiation and progression. Notably, tumors often exhibit reduced expression of mature miRNAs. In CRC research, miRNAs offer potential as diagnostic biomarkers and therapeutic targets. Specific miRNA profiles could serve as non-invasive tools for early CRC detection and risk assessment. Additionally, miRNA-based therapies present a promising approach for targeted cancer treatment by modulating miRNA expression. However, challenges related to delivery systems and long-term safety must be addressed to fully harness their therapeutic potential.

Cannabis use and cyclical vomiting syndrome: An open debate.

INTRODUCTION: Cyclical vomiting syndrome (CVS) carries a significant financial burden on the U.S. healthcare system due to the recurrent emergency department visits and inpatient hospitalizations. We aimed to update the literature on the predictors of hospital utilization and readmission among individuals admitted with CVS. METHODS: This is a retrospective nationwide study of patients hospitalized with a primary diagnosis of CVS. Using weighted data from the National Inpatient Sample (NIS) and the National Readmission Database (NRD), we conducted a multivariate regression analysis to assess predictors of length of stay (LOS), and 30-day readmission. RESULTS: Primary admissions for CVS totaled 35,055 in the NIS, and 31,240 in the NRD. 2012 patients (6.4%) were readmitted within 30 days. On multivariate regression, cannabis use was associated with reduced LOS (adjusted Mean Difference (aMD) = -0.53 days, 95% CI: -0.68 to -0.38), and 30-day readmissions (adjusted Hazard Ratio (aHR) = 0.63, 95% CI: 0.54-0.73). DISCUSSION: Cannabis use among CVS admissions was associated with reduced LOS and 30-day readmissions; these results could be in fact driven by Cannabis Hyperemesis Syndrome (CHS)-related hospitalizations and the effect of cannabis cessation on decreased symptomatology. ICD-10 coding for CHS should be transitioned to specific codes to improve the differentiation between CVS and CHS-related hospitalizations.

Impact of COVID-19 on Acute Myocardial Infarction: A National Inpatient Sample Analysis.

COVID-19 has been associated with a higher incidence of acute myocardial infarction and related complications. We sought to assess the impact of COVID-19 diagnosis on hospitalizations with an index admission of AMI. The National inpatient sample 2020 was queried for hospitalizations with an index admission of AMI, further stratified for admissions with and without COVID-19. The 2 groups' mortality, procedure, and complication rates were compared using suitable statistical tests. Multivariate regression analysis was further performed to study the impact of COVID-19 on mortality as the primary outcome and length of stay and total hospital cost as secondary outcomes. A total of 555,540 admissions for AMI were identified, of which 5818 (1.04%) had concomitant COVID-19. Hospitalizations in the COVID-19 cohort of both groups had a lower procedure rate for coronary angiography. Thrombolysis use was higher in the STEMI patients with COVID-19. Most cardiac complications in AMI patients were higher when infected with SARS-CoV-2. Multivariate regression analysis revealed that COVID-19 led to higher odds of mortality and total length of stay in AMI hospitalizations. COVID-19 portends a worse prognosis in hospitalizations with AMI. These admissions have a significantly higher mortality rate and increased complications.