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Development of a Transcriptional Biosensor for Hydrogen Sulfide that Functions under Aerobic and Anaerobic Conditions.

Hydrogen sulfide (H2S) is a gaseous gut metabolite with disputed effects on gastrointestinal health. Monitoring H2S concentration in the gut would provide insight into its role in disease, but is complicated by sulfide's reactivity and volatility. Here we develop a transcriptional sulfide biosensor in E. coli. The sensor relies on enzymatic oxidation of sulfide catalyzed by a sulfide:quinone reductase (Sqr) to polysulfides, which bind to the repressor SqrR, triggering unbinding from the promoter and transcription of the reporter. Through promoter engineering and improving soluble SqrR expressi

Gelatin Methacryloyl Xerogel Puncture Implants Loaded with Cu0.5Mn2.5O4 Nanoparticles Synergizes Cuproptosis and STING Activation for Enhanced Breast Cancer Immunotherapy.

The immunosuppressive niche of the breast cancer microenvironment and the vascular basement membrane significantly hinder the efficacy of nanoparticle-based antitumor immunotherapy delivered via the vascular system. This study describes the design of a puncture-delivered tumor implant, utilizing a photo-cross-linked gelatin methacryloyl hydrogel as the matrix, loaded with Cu0.5Mn2.5O4 nanoparticles (CMO NPs) and monomethyl fumarate (MMF), enabling the sustained release of nanoparticles through matrix metalloproteinase-responsive degradation. Mechanistically, CMO NPs induce cuproptosis and immu

Терапевтические достижения в педиатрии с множественным склерозом.

Педиатрический множественный склероз (POMS) является хроническим и иммунным расстройством, которое влияет на центральную нервную систему детей и подростков. Примерно 3-10% пациентов, страдающих синдромом MS, имеют место до достижения 18-летнего возраста. Подавляющее большинство случаев заболевания педиатрическим синдромом MS характеризуется повторной эрозией с высоким уровнем заболеваемости. Пациенты педиатрии, страдающие синдромом MS, традиционно проходили лечение без маркировки с различной степенью успеха. С одобрением многих новых методов лечения для взрослых МР быстро начали появляться аль

Совпадение в полном тексте источника
… Pediatric multiple sclerosis is treated with a variety of disease-modifying therapies, including interferons, glatiramer acetate, fumarates, teriflunomide, anti-CD52 and CD20 monoclonal antibodies, natalizumab, and fingolimod. 4. … Fumarates Dimethyl Fumarate (DMF) DMF (Tecfidera) is a fumaric acid ester that affects the nervous and immune systems in a variety of ways [ 58 ]. …

Concomitant medication, comorbidity and survival in patients with breast cancer.

Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associa

Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displaye

Cytosolic PEPCK deficiency caused by a novel homozygous frame-shift variant presenting as resolved hypoglycemia and acute liver failure at birth.

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme encoded by the PCK1 gene and plays a rate limiting step in gluconeogenesis occurring mainly in the liver during prolonged fasting. Biallelic deficiency of this enzyme results in a rare inborn error of metabolism disorder (OMIM # 261680). The main clinical and laboratory manifestations include fasting hypoglycemia and lactic acidosis with urinary excretion of Tricarboxylic Acid (TCA) cycles metabolites, particularly fumarate. The initial presentation varies between individuals in terms of age at initial presentation and clinical m

Comparative analysis of LC-HRMS profiling, ATR FT-IR spectroscopy, antioxidant, anti-diabetic, and anti-tyrosinase activities of extracts from Cotoneaster frigidus Wall. Ex Lindl. "Cornubia" fruit.

The antioxidant, total phenolic, flavonoid, and anthocyanidin properties of extracts prepared from Cotoneaster frigidus Wall. ex Lindl. "Cornubia" fruit were examined. In addition, the phenolic profile was analyzed using LC-HRMS, and the surface morphological features were studied using ATR FT-IR. Additionally, the inhibitory potential of the extracts on tyrosinase and α-glucosidase/α-amylase was tested. The highest antioxidant activity values were found in ethyl acetate and methanol extracts. The methanol extract was found to be rich in TFC, TPC and TPA. In the research conducted to designate

Metabolic alterations in hereditary and sporadic renal cell carcinoma.

Kidney cancer is the seventh leading cause of cancer in the world, and its incidence is on the rise. Renal cell carcinoma (RCC) is the most common form and is a heterogeneous disease comprising three major subtypes that vary in their histology, clinical course and driver mutations. These subtypes include clear cell RCC, papillary RCC and chromophobe RCC. Molecular analyses of hereditary and sporadic forms of RCC have revealed that this complex and deadly disease is characterized by metabolic pathway alterations in cancer cells that lead to deregulated oxygen and nutrient sensing, as well as im

Infantile Fructose-1,6-Bisphosphatase Deficiency Masquerading as Mitochondriopathy.

Fructose-1,6-bisphosphatase 1 (FBP1) deficiency is a rare autosomal recessive disorder of gluconeogenesis. Affected children present with severe hypoglycemia and lactic acidosis in infancy. We report a case of a female child, aged one year and six months, born out of a third-degree consanguineous marriage, who initially presented with sudden-onset vomiting episodes and failure to thrive. Despite a clinical suspicion of mitochondrial disorder, biochemical investigations revealed elevated levels of alanine, glycine, lactic acid, pyruvic acid, 3-hydroxy isovaleric acid, fumaric acid, and 4-hydrox

Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis.

Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation. AspA-dependent growth adv

Design, synthesis, and repurposing of O6-aminoalkyl-sulfuretin analogs towards discovery of potential lead compounds as antileishmanial agents.

Up to date, there are still significantly unmet clinical needs for treatment of the fatal visceral leishmaniasis; a neglected tropical disease. Herein, a recently reported antileishmanial hit sulfuretin analog suffering from a low potency and a problematic aqueous solubility that hindered further development was used as a starting point. A mitigation rational via incorporation of O6-aminoalkyl moiety suggest structures analogous to literature-known compounds as cholinesterase inhibitors. Consequently, preparation and repurposing of a library of these compounds unveiled their potential activity

Acquired Fanconi Syndrome from Tenofovir Treatment in a Patient with Hepatitis B.

Fanconi syndrome is a rare disease of generalized proximal tubule dysfunction which can be acquired secondary to certain medications, including tenofovir, a commonly used hepatitis B treatment. Signs and symptoms of ensuing renal wasting can be severe but vague, leading to potentially avoidable invasive investigations and delays in diagnosis. We present a case of a 62-year-old female with chronic hepatitis B on tenofovir treatment who was found to have subacute weakness, anorexia, and weight loss. She underwent extensive investigations including computed tomography (CT) imaging, bronchoscopy,

Biktarvy for the treatment of HIV infection: Progress and prospects.

Bictegravir (BIC), a second-generation integrase strand-transfer inhibitor (INSTI) with high resilience to INSTI-resistance mutations, is integrated as a key component of Biktarvy® - a fixed-dose once-daily triple-drug regimen of bictegravir (BIC), emtricitabine (FTC) plus tenofovir alafenamide (TAF). Based on the accumulated evidence from HIV clinical trials and real-world studies, the clinical effectiveness of BIC + FTC + TAF has been proven non-inferior to other fixed-dose once-daily combinations such as dolutegravir + FTC + TAF and dolutegravir + abacavir + lamivudine. Biktarvy also shows

A case report of clinical implications of a delayed antiretroviral therapy switch in a patient with multiple treatment interruptions.

The Namibia national antiretroviral therapy guidelines recommend that patients living with HIV who interrupt antiretrovirals and in the process disengage from care be restarted on their usual antiretroviral therapy regimen upon return. We introduce a 39-year-old male patient on first-line antiretroviral therapy, namely, tenofovir disoproxil fumarate, lamivudine and efavirenz, from 2015 to 2019 (4 years), who returned to care after the fourth episode of interrupting his treatment, though his adherence to antiretroviral therapy was deemed poor. Thus, he presented with severe immunosuppression an

Static and group-based trajectory analyses of factors associated with non-adherence in patients with multiple sclerosis newly-initiating once- or twice-daily oral disease-modifying therapy.

BackgroundIncreased understanding of adherence may facilitate optimal targeting of interventions.ObjectiveTo utilize group-based trajectory modeling (GBTM) to understand longitudinal patterns of adherence and factors associated with non-adherence in patients with multiple sclerosis (MS) newly-initiating once-/twice-daily oral disease-modifying therapy (DMT) (fingolimod, dimethyl fumarate, or teriflunomide).MethodsCommercial plan data were analyzed using proportion of days covered (PDC) to evaluate factors associated with non-adherence. GBTM clustered patient subgroups with similar longitudinal

Safety of current antiviral drugs for chronic hepatitis B.

INTRODUCTION: Oral nucleos(t)ide analogues (NUCs) are recommended as first-line therapy for chronic hepatitis B (CHB) due to higher HBV-DNA suppression rates and safety profile. Long-term treatment with NUCs is often necessary to achieve durable viral suppression. AREAS COVERED: This review provides an overview of the long-term safety data that have become available since entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were first approved, and recent data on tenofovir alafenamide (TAF) in patients with CHB. EXPERT OPINION: NUCs generally show remarkable safety in patients taking them

Acute hepatitis B in pregnancy with surprisingly rapid clearance of serum HBs antigen associated with a favourable outcome.

Acute hepatitis B (AHB) is usually asymptomatic, but it can progress to chronic hepatitis B (HB) defined by HB surface antigen (HBsAg) persisting beyond 6 months. Nevertheless, the delay of HBsAg seroclearance is not well-defined. During pregnancy, the immune system of the pregnant women is altered and delayed HBsAg loss can be observed, leading to chronic infection. Here, we present an uncommon case of AHB in a pregnant woman in whom rapid HBsAg seroclearance (52 days after AHB) was associated with a favourable outcome (no injury to liver). This patient received tenofovir disoproxil fumarate

Tribute to John C. Martin at the Twentieth Anniversary of the Breakthrough of Tenofovir in the Treatment of HIV Infections.

At Bristol-Myers (BM) (1985-1990), John C. Martin started his HIV career with directing the clinical development of didanosine (ddI) and stavudine (d4T). During this period, he became aware of the acyclic nucleoside phosphonates (ANPs), such as (S)-HPMPA and PMEA, as potential antiviral drugs. Under his impulse, BM got involved in the evaluation of these ANPs, but the merger of BM with Squibb (to become BMS) incited John to leave BM and join Gilead Sciences, and the portfolio of the ANPs followed the transition. At Gilead, John succeeded in obtaining the approval from the US FDA for the use of

Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis.

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial

Mangiferin improves hepatic damage-associated molecular patterns, lipid metabolic disorder and mitochondrial dysfunction in alcohol hepatitis rats.

This study was conducted to investigate the beneficial effects and possible mechanism of action of mangiferin (MF) in alcohol hepatitis (AH) rats. Building on our previous study, the damage-associated molecular patterns (DAMPs), lipid metabolic disorder and mitochondrial dysfunction were investigated. MF effectively regulated the abnormal liver function, the levels of alcohol, FFAs and metal elements in serum. More importantly, MF improved the expression levels of mRNA and protein of PPAR-γ, OPA-1, Cav-1, EB1, NF-κB p65, NLRP3, Cas-1 and IL-1β, and decreased the positive protein expression rat