Enhancing CNS mitophagy: drug development and disease-relevant models.

Mitophagy, the selective degradation of mitochondria, is impaired in many neurodegenerative diseases (NDs), resulting in an accumulation of dysfunctional mitochondria and neuronal damage. Although enhancing mitophagy shows promise as a therapeutic strategy, the clinical significance of mitophagy activators remains uncertain due to limited understanding and poor representation of mitophagy in the central nervous system (CNS). This review explores recent insights into which mitophagy pathways to target and the extent of modulation necessary to be therapeutic towards NDs.

Enrichment of Polycyclic Aromatic Hydrocarbon (PAH)-Degrading Strictly Anaerobic Sulfate-Reducing Cultures from Contaminated Soil and Sediment.

Sulfate-reducing bacteria (SRB) are crucial players in global biogeochemical cycling and some have been implicated in the anaerobic biodegradation of organic pollutants, including recalcitrant and hazardous polycyclic aromatic hydrocarbons (PAHs). Obtaining PAH-degrading SRB cultures for laboratories is of paramount importance in the development of the young field of anaerobic biodegradation of PAHs. SRB grow exceptionally slowly on PAH substrates and are highly sensitive to oxygen.

Anoxygenic phototrophic purple non-sulfur bacteria: tool for bioremediation of hazardous environmental pollutants.

The extraordinary metabolic flexibility of anoxygenic phototrophic purple non-sulfur bacteria (PNSB) has been exploited in the development of various biotechnological applications, such as wastewater treatment, biohydrogen production, improvement of soil fertility and plant growth, and recovery of high-value compounds. These versatile microorganisms can also be employed for the efficient bioremediation of hazardous inorganic and organic pollutants from contaminated environments. Certain members of PNSB, especially strains of Rhodobacter sphaeroides and Rhodopseudomonas palustris, exhibit efficient remediation of several toxic and carcinogenic heavy metals and metalloids, such as arsenic, cadmium, chromium, and lead.

Anaerobic biodegradation of phenanthrene and pyrene by sulfate-reducing cultures enriched from contaminated freshwater lake sediments.

Our current understanding of the susceptibility of hazardous polycyclic aromatic hydrocarbons (PAHs) to anaerobic microbial degradation is very limited. In the present study, we obtained phenanthrene- and pyrene-degrading strictly anaerobic sulfate-reducing enrichments using contaminated freshwater lake sediments as the source material. The highly enriched phenanthrene-degrading culture, MMKS23, was dominated (98%) by a sulfate-reducing bacterium belonging to the genus Desulfovibrio.

Efficient bioremediation of laboratory wastewater co-contaminated with PAHs and dimethylformamide by a methylotrophic enrichment culture.

A methylotrophic enrichment culture, MM34X, has been assessed for its exceptional ability in biodegradation of dimethylformamide (DMF) and bioremediation of laboratory wastewater (LWW) co-contaminated with polycyclic aromatic hydrocarbons (PAHs). The culture MM34X tolerated high concentrations of DMF and efficiently degraded 98% of 20,000 mg L DMF within 120 h. LWW bioremediation was performed in stirred bottle laboratory-scale bioreactor.

Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.

The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB innate immune axis is activated and resolved remain poorly understood.

Efficient bioremediation of PAHs-contaminated soils by a methylotrophic enrichment culture.

Bioaugmentation effectively enhances microbial bioremediation of hazardous polycyclic aromatic hydrocarbons (PAHs) from contaminated environments. While screening for pyrene-degrading bacteria from a former manufactured gas plant soil (MGPS), the mixed enrichment culture was found to be more efficient in PAHs biodegradation than the culturable pure strains. Interestingly, analysis of 16S rRNA sequences revealed that the culture was dominated by a previously uncultured member of the family Rhizobiaceae.

Anaerobic Degradation of Naphthalene and Pyrene by Sulfate-Reducing Cultures Enriched from Former Manufactured Gas Plant Soil.

Biodegradation of polycyclic aromatic hydrocarbons (PAHs) under completely anaerobic sulfate-reducing conditions is an energetically challenging process. To date, anaerobic degradations of only two-ringed naphthalene and three-ringed phenanthrene by sediment-free and enriched sulfate-reducing bacteria have been reported. In this study, sulfate-reducing enrichment cultures capable of degrading naphthalene and four-ringed PAH, pyrene, were enriched from a contaminated former gas plant site soil.

Pythiosis in a patient with Acute Myeloid Leukemia: Diagnosis and clinical course.

Pythiosis, caused by Pythium insidiosum (a fungal-like stramenipila, a group of eukaryotes away from the true fungi). Pythium insidiosum causes rare human and animal infections. Transmission from animals to human is yet to be reported.

Innate immunity and inflammophagy: balancing the defence and immune homeostasis.

Extensive crosstalk exists between autophagy and innate immune signalling pathways. The stimuli that induce pattern recognition receptor (PRR)-mediated innate immune signalling pathways, also upregulate autophagy. The purpose of this increased autophagy is to eliminate the stimuli and/or suppress the inflammatory pathways by targeted degradation of PRRs or intermediary proteins (termed 'inflammophagy').

Gonadorelins adherence in prostate cancer: A time-series analysis of England's national prescriptions during the COVID-19 pandemic (from Jan 2019 to Oct 2020).

Objective: To examine the effect of the COVID-19 pandemic on gonadorelin analogue prescription for community patients in England.

Materials And Methods: We included data from all primary-care patients who had relevant prescriptions dispensed in the community in England. Descriptive statistics and interrupted time series analysis over 22 months (15 months before and 7 months after lockdown) was evaluated.

Ensemble of Deep Learning Models for Sleep Apnea Detection: An Experimental Study.

Sleep Apnea is a breathing disorder occurring during sleep. Older people suffer most from this disease. In-time diagnosis of apnea is needed which can be observed by the application of a proper health monitoring system.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

Purpose: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN).

Methods: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy).

Impact of polycystic ovary syndrome on quality of life of women in correlation to age, basal metabolic index, education and marriage.

Polycystic ovary syndrome (PCOS) is the major endocrine related disorder in young age women. Physical appearance, menstrual irregularity as well as infertility are considered as a sole cause of mental distress affecting health-related quality of life (HRQOL). This prospective case-control study was conducted among 100 PCOS and 200 healthy control cases attending tertiary care set up of AIIMS, Patna during year 2017 and 2018.

Emerging Role of Terpenoids for the Treatment of Cancer: A Review.

Aim: Terpenes are natural compounds found in several organisms belonging to the animal and plant kingdom, therefore, constitute the largest class of natural products and were a rich reservoir of candidate compounds for drug discovery. The review aims to focus on the extensive potential of the anti-cancer terpenoid components obtained from natural plant species which may lead to the development of a variety of derived terpenoids moieties.

Method: Literature survey has been carried out to determine the potential of terpenoids.

IRGM links autoimmunity to autophagy.

IRGM is a genetic risk factor for several autoimmune diseases. However, the mechanism of IRGM-mediated protection in autoimmunity remains undetermined. The abnormal activation of type I interferon (IFN) response is one of the significant factors in the pathogenesis of several autoimmune diseases.

Electronic cigarette extract induced toxic effect in iPS-derived cardiomyocytes.

Background: Cigarette smoking is an important risk factor for cardiac diseases. In the current study, we sought to assess the effect of electronic cigarette extract (ECE) and conventional cigarette smoke extract (CSE) on cardiomyocytes.

Methods: iPSCs-derived cardiomyocytes were used in the study to evaluate cellular toxicities.

Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response.

Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response.

Immunomodulation-mediated anticancer activity of a novel compound from Brugmansia suaveolens leaves.

Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis.

TGF-β induces a heart failure phenotype via fibroblasts exosome signaling.

Purpose: The mechanisms for persistent and progressive loss of myocardial function in advanced heart failure (HF) remain incompletely characterized. In the current study, we sought to determine the impact of TGF-β on fibroblasts transcriptional profiles and assess if exosomes from TGF-β treated fibroblasts could induce a heart failure phenotype in co-cultured cardiomyocytes.

Method: Normal heart fibroblasts were treated with TGF-β with a final conc.

Antibody drug conjugates against the receptor for advanced glycation end products (RAGE), a novel therapeutic target in endometrial cancer.

Background: The treatment of endometrial cancer (EC), the most common gynecological cancer, is currently hampered by the toxicity of current cytotoxic agents, meaning novel therapeutic approaches are urgently required.

Methods: A cohort of 161 patients was evaluated for the expression of the receptor for advanced glycation end products (RAGE) in endometrial tissues. The present study also incorporates a variety of in vitro methodologies within multiple cell lines to evaluate RAGE expression and antibody-drug conjugate efficacy, internalisation and intercellular trafficking.

Relative potency of different generic brands of meropenem, colistin and fosfomycin: Implications for antimicrobial therapy and antimicrobial formulary.

There is a need of a relatively simple and inexpensive method for the determination of relative potency of various generic brands of antibiotics in comparison to original products. The current study describes an agar diffusion method which can be performed in any microbiology laboratory, is cheap (costs $2 per test) and its results can be available after overnight incubation. The results show that neither all generics are reliable nor are all generic antibiotics of poor quality.

IRGM restrains NLRP3 inflammasome activation by mediating its SQSTM1/p62-dependent selective autophagy.

IRGM is an established genetic risk factor for Crohn disease (CD) and several other inflammatory disorders. However, the mechanisms employed by IRGM to restrain the inflammation are not known. In our recent study, we showed that IRGM negatively regulates NLRP3 inflammasome activation.