Nimbolide attenuates hepatocellular carcinoma by regulating miRNAs 21, 145 and 221 and their target gene expression.

Background And Aims: MicroRNAs (miRNAs) are becoming progressively emerging in cancer research from an etiologic and curative point of view. Several miRNAs act as oncogenes or tumor suppressors, which are dysregulated in numerous cancers. Our previous studies have established that nimbolide (a bioactive terpenoid from neem) attenuated hepatocellular carcinoma (HCC) through various mechanisms in mice.

NOSTRIN is an emerging negative regulator of decompensated cirrhotic patients with portal hypertension.

Background And Aims: Decreased nitric oxide (NO) bioavailability in a cirrhotic liver contributes to high intrahepatic vascular resistance (IHVR) and portal hypertension (PHT). Nostrin is an inhibitory protein of NO synthesising enzyme endothelial NO synthase (eNOS), shown to increase in cirrhosis with PHT, however, the precise molecular mechanism is poorly documented. This study aimed to elucidate the role of Nostrin and associated derangement in hepatic NO generation in cirrhotic liver.

Dynamic occupancy modelling of Asian elephants (Elephas maximus) reveals increasing landscape use in Nepal.

Large mammals with general habitat needs can persist throughout mixed used landscapes, however, human-wildlife conflict frequently leads to their restriction to protected areas. Conservation efforts, especially for reducing conflicts with humans, can enhance tolerance of humans towards species like Asian elephants (Elephas maximus) in human-dominated landscapes. Here, we examine how elephant use in the Chure Terai Madhesh Landscape (CTML) covering the entire elephant range of Nepal changed between 2012 and 2020 in relationship to protection status and environmental conditions.

Overview of Methamphetamine-Associated Pulmonary Arterial Hypertension.

Topic Importance: The global surge in methamphetamine use is a critical public health concern, particularly due to its robust correlation with methamphetamine-associated pulmonary arterial hypertension (MA-PAH). This association raises urgent alarms about the potential escalation of MA-PAH incidence, posing a significant and imminent challenge to global public health.

Review Findings: This comprehensive review meticulously explores MA-PAH, offering insights into its epidemiology, pathophysiology, clinical presentation, diagnostic intricacies, and management strategies.

Notch3 deletion regulates HIV-1 gene expression and systemic inflammation to ameliorate chronic kidney disease.

Antiretroviral therapy (ART) has decreased HIV-1 associated morbidity. However, despite ART, immune cells remain latently infected and slowly release viral proteins, leading to chronic inflammation and HIV-1 associated comorbidities. New strategies are needed to target viral proteins and inflammation.

Polymeric immunoglobulin receptor and galectin-3-binding protein are raised in biliary atresia: Reveals a proteomic-based study.

To identify and evaluate differentially expressed plasma proteins in biliary atresia (BA), we performed plasma proteome profiling using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 20 patients with BA and 10 control children. Serological assays validated the most significant and highly upregulated proteins in a cohort of 45 patients and 15 controls. Bioinformatics tools were used for functional classification and protein-protein interactions of differentially expressed proteins (DEPs).

HIV and Drug Use: A Tale of Synergy in Pulmonary Vascular Disease Development.

Over the past two decades, with the advent and adoption of highly active anti-retroviral therapy, HIV-1 infection, a once fatal and acute illness, has transformed into a chronic disease with people living with HIV (PWH) experiencing increased rates of cardio-pulmonary vascular diseases including life-threatening pulmonary hypertension. Moreover, the chronic consequences of tobacco, alcohol, and drug use are increasingly seen in older PWH. Drug use, specifically, can have pathologic effects on the cardiovascular health of these individuals.

Association of Micronutrients with Tuberculosis Development in HIV Infected Patients.

Human immunodeficiency virus (HIV) infection associated with weakened immune system due to decreased CD4 T cell count favors development of tuberculosis. Effector immune responses are also associated with micronutrient status due to their prominent role in maintaining immune functions. Micronutrient deficiencies are quite common among HIV patients that further result into compromised immunity thus making the conditions even more favorable for mycobacteria to establish disease.

Placental expression of striatin & endothelial nitric oxide synthase in women with & without pre-eclampsia.

Background & Objectives: Striatin is a multi-domain scaffolding protein essential for activating endothelial nitric oxide synthase (eNOS). However, its role in pre-eclampsia remains use explored. Hence, this study aimed to investigate the association between striatin and eNOS in regulating nitric oxide (NO) production in the placenta of women with and without pre-eclampsia.

Persistent circulation of soluble and extracellular vesicle-linked Spike protein in individuals with postacute sequelae of COVID-19.

SARS-CoV-2, the causative agent of COVID-19 disease, has resulted in the death of millions worldwide since the beginning of the pandemic in December 2019. While much progress has been made to understand acute manifestations of SARS-CoV-2 infection, less is known about post-acute sequelae of COVID-19 (PASC). We investigated the levels of both Spike protein (Spike) and viral RNA circulating in patients hospitalized with acute COVID-19 and in patients with and without PASC.

Higher intensity exercise reduces disability more than lower intensity exercise in adults with chronic low back pain: A systematic review and meta-analysis.

Background: Intensity is an important determinant of physiological adaptations and health benefits of exercise, but the role of exercise intensity on improving outcomes in people with chronic low back pain (CLBP) is unclear. This systematic review aimed to determine the effect of higher versus lower intensity exercise intensity on pain, disability, quality of life and adverse events in people with CLBP.

Methods: Six databases and four clinical trial registries were searched from inception to 21 December 2022, for randomised controlled trials that compared two or more exercise intensities in adults with CLBP.

Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities.

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its sublineages pose a new challenge to healthcare systems worldwide due to its ability to efficiently spread in immunized populations and its resistance to currently available therapies. COVID-19, although targeting primarily the respiratory system, is also now well established that later affects every organ in the body. Most importantly, despite the available therapy and vaccine-elicited protection, the long-term consequences of viral infection in breakthrough and asymptomatic individuals are areas of concern.

Role of zonula occludens in gastrointestinal and liver cancers.

A growing body of evidence suggests that tight junction (TJ) proteins play a crucial role in the pathogenesis of various diseases, including gastrointestinal (GI) cancer and hepatocellular carcinoma (HCC). TJ proteins primarily maintain the epithelial and endothelial cells intact together through integral proteins however, recent reports suggest that they also regulate gene expression necessary for cell proliferation, angiogenesis, and metastasis through adapter proteins such as zonula occludens (ZO). ZO proteins are membrane-associated cytosolic scaffolding proteins that modulate cell proliferation by interacting with several transcription factors.

Altered proteome in translation initiation fidelity defective eIF5 mutant causes oxidative stress and DNA damage.

The recognition of the AUG start codon and selection of an open reading frame (ORF) is fundamental to protein biosynthesis. Defect in the fidelity of start codon selection adversely affect proteome and have a pleiotropic effect on cellular function. Using proteomic techniques, we identified differential protein abundance in the translation initiation fidelity defective eIF5 mutant that initiates translation using UUG codon in addition to the AUG start codon.

Nimbolide attenuates gut dysbiosis and prevents bacterial translocation by improving intestinal barrier integrity and ameliorating inflammation in hepatocellular carcinoma.

Gut microbiota imbalance plays a key pathological role in hepatocellular carcinoma (HCC) progression; however, the mechanism is poorly understood. We previously showed nimbolide impede tumor development by improving hepatic tight junction (TJ) proteins expression and attenuating inflammation in HCC mice. Here, we aimed to study the role of nimbolide in regulating gut microbiota imbalance and bacterial translocation (BT) through modulating intestinal TJ proteins in an experimental hepatocarcinogenesis.

Tracking forest loss and fragmentation between 1930 and 2020 in Asian elephant (Elephas maximus) range in Nepal.

Forest cover is the primary determinant of elephant distribution, thus, understanding forest loss and fragmentation is crucial for elephant conservation. We assessed deforestation and patterns of forest fragmentation between 1930 and 2020 in Chure Terai Madhesh Lanscape (CTML) which covers the entire elephant range in Nepal. Forest cover maps and fragmentation matrices were generated using multi-source data (Topographic maps and Landsat satellite images of 1930, 1975, 2000, and 2020) and spatiotemporal change was quantified.

Patterns and determinants of elephant attacks on humans in Nepal.

Attacks on humans by Asian elephant () is an extreme form of human-elephant conflict. It is a serious issue in southern lowland Nepal where elephant-related human fatalities are higher than other wildlife. Detailed understanding of elephant attacks on humans in Nepal is still lacking, hindering to devising appropriate strategies for human-elephant conflict mitigation.

Nimbolide inhibits tumor growth by restoring hepatic tight junction protein expression and reduced inflammation in an experimental hepatocarcinogenesis.

Background: Altered tight junction (TJ) proteins are correlated with carcinogenesis and tumor development. Nimbolide is a tetranotriterpenoid that has been shown to have antioxidant and anti-proliferative properties; however, its anticancer effects and molecular mechanism in hepatocellular carcinoma (HCC) remains obscure.

Aim: To investigate the effect of nimbolide on TJ proteins, cell cycle progression, and hepatic inflammation in a mouse model of HCC.

Ribosomal mutation in helix 32 of 18S rRNA alters fidelity of eukaryotic translation start site selection.

The 40S ribosome plays a critical role in start codon selection. To gain insights into the role of its 18S rRNA in start codon selection, a suppressor screen was performed that suppressed the preferential UUG start codon recognition (Suppressor of initiation codon: Sui phenotype) associated with the eIF5 mutant. The C1209U mutation in helix h32 of 18S rRNA was found to suppress the Sui and Gcn (failure to derepress GCN4 expression) phenotype of the eIF5 mutant.

Increased systemic zonula occludens 1 associated with inflammation and independent biomarker in patients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a frequent type of primary liver cancer, and its prevalence is increasing worldwide. Indeed, the underlying molecular mechanism is not well understood. Previous studies have shown evidence that tight junction (TJ) components were correlated with carcinogenesis and tumor development.

Increased advanced glycation end product specific fluorescence in repeatedly heated used cooking oil.

Repeated heating of cooking oils is known to cause their degradation and generation of toxins. Dietary Advanced glycation end products (dAGEs) are formed when the foods are cooked in dry heat at very high temperatures. dAGEs are believed to contribute significantly to total pool of AGEs in body.