Tumor Heterogeneity Shapes Survival Dynamics in Drug-Treated Cells, Revealing Size-Drifting Subpopulations.

The goal of this project was to demonstrate that subpopulations of cells in tumors can uniquely fluctuate in size in response to environmental conditions created during drug treatment, thereby acting as a dynamic "rheostat" to create a favorable tumor environment for growth. The cancer modeling used for these studies was subpopulations of melanoma cells existing in cultured and tumor systems that differed in aldehyde dehydrogenase (ALDH) activity. However, similar observations were found in other cancer types in addition to melanoma, making them applicable broadly across cancer.

Identification of Novel Isatin Derivative Bearing a Nitrofuran Moiety as Potent Multi-Isoform Aldehyde Dehydrogenase Inhibitor.

Aldehyde dehydrogenases (ALDHs) are a family of enzymes that aid in detoxification and are overexpressed in several different malignancies. There is a correlation between increased expression of ALDH and a poor prognosis, stemness, and resistance to several drugs. Several ALDH inhibitors have been generated due to the crucial role that ALDH plays in cancer stem cells.

Concomitant Pulmonary Aspergillosis Following Severe COVID-19.

This case report discusses an atypical complication of COVID-19 pneumonia in a 68-year-old male patient, distinguished by the development of cavitary lung disease and a subsequent incidence of invasive pulmonary aspergillosis (IPA). This adverse development transpired following a prolonged hospitalization and an extensive course of corticosteroid therapy post-COVID-19 pneumonia. This case accentuates the importance of vigilance in observing patients with severe COVID-19 pneumonia for potential opportunistic infections, particularly given the inherent risks associated with prolonged corticosteroid therapy.

Inhibition of melanogenesis by 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone via suppressing the activity of cAMP response element-binding protein (CREB) and nuclear exclusion of CREB-regulated transcription coactivator 1 (CRTC1).

Exposure to Ultraviolet radiation or α-melanocyte-stimulating hormone (α-MSH) stimulates the Cyclic Adenosine Monophosphate/Protein Kinase A signalling pathway, which leads to the synthesis and deposition of melanin granules in the epidermis. Skin pigmentation is the major physiological defence against inimical effects of sunlight. However, excessive melanin production and accumulation can cause various skin hyperpigmentation disorders.

Dereplication Based Strategy for Rapid Identification and Isolation of a Novel Anti-inflammatory Flavonoid by LCMS/MS from .

is a folkloric medicinal plant, well known for its tremendous medicinal properties such as curing epilepsy, ulcers, and urinary problems. The aim of the present study was to apply the dereplication strategy on the ethanol extract of with potent anti-inflammatory activity for the rapid identification and isolation of novel bioactive molecules to aid the drug discovery process. An integrated approach using liquid chromatography-mass spectrometry (LCMS) followed by preparative high-performance liquid chromatography (HPLC) was used for the isolation of potent molecules from the anti-inflammatory extract of Purity of the compounds (>98.

Co-infection with Pseudomonas aeruginosa impacts virulence of Staphylococcus aureus and intensifies the severity of infection.

Multi-specie infections display diverse interactions among pathogens that influence the severity of disease. Staphylococcus aureus and Pseudomonas aeruginosa are the two most important opportunistic, nosocomial and drug-resistant pathogens. Poly-infections due to S.

Trigonelline prevents high cholesterol and high fat diet induced hepatic lipid accumulation and lipo-toxicity in C57BL/6J mice, via restoration of hepatic autophagy.

Non-alcoholic fatty liver disease (NAFLD) is often linked with impaired hepatic autophagy. Here, we studied the alterations in hepatocellular autophagy by high cholesterol and high-fat diet (HC-HF) diet in C57BL/6J mice, and by palmitic acid (PA), in AML-12 and HepG2 cells. Further, we analysed role of Trigonelline (TG), a plant alkaloid, in preventing NAFLD, by modulating autophagy.

Anti-inflammatory potential of hentriacontane in LPS stimulated RAW 264.7 cells and mice model.

Hentriacontane, has various pharmacological effects including anti-inflammatory, antitumor and antimicrobial activities. Its anti-inflammatory potential has been demonstrated in peritoneal macrophages. However detailed studies on other models elucidating the mechanistic description of the mode of action has not been done.

Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus.

Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products.

Cardiac lymphangioma presenting as intrapericardial cystic mass.

Cystic lymphangioma usually confined to head and neck is a well-recognized tumor that occurs during childhood. However, a cardiac lymphangioma is exceptionally uncommon and a particularly rare form of disease. We report a case of cystic lymphangioma arising from the right ventricular wall, and presenting as pericardial mass in a young female, who presented with a history of exercise intolerance in the form of breathlessness on exertion and palpitations.

Presence of virulent Newcastle disease virus in vaccinated chickens in farms in Pakistan.

One year after a virulent Newcastle disease virus (vNDV) outbreak in Pakistan, the causative strain was present in vaccinated chickens of multiple farms despite the existence of high-average NDV-specific antibody titers (>4.75 log2). The data suggest a possible role of vaccinated birds as reservoirs of vNDV.

Comparative efficacy of long-acting muscarinic antagonists in preventing COPD exacerbations: a network meta-analysis and meta-regression.

Background: We hypothesized a class effect of currently available long-acting muscarinic antagonists (LAMAs; i.e., tiotropium as a dry powder inhaler or a soft mist inhaler, aclidinium bromide, and glycopyrronium) in preventing chronic obstructive pulmonary disease (COPD) exacerbations.

Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis.

Background: A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis.

Mortality benefit of vasopressor and inotropic agents in septic shock: a Bayesian network meta-analysis of randomized controlled trials.

Objective: The choice of vasopressor in septic shock has been a matter of debate. The purpose of this study was to systematically review overall evidence of vasopressor and inotropic agents in septic shock using a Bayesian network meta-analysis.

Methods: Databases, including Medline, Scopus, CINAHL, and Google Scholar were searched to identify relevant studies.

Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Background: Roflumilast, a phosphodiesterase 4 inhibitor, has been shown to improve lung function and reduce exacerbation rates, but is associated with adverse events (AEs). The purpose of this study was to systematically review the clinical effectiveness and safety of roflumilast.

Methods: A systematic search was made of MEDLINE, Cochrane trials database, DARE and CINAHL.

Characterization of H5N1 highly pathogenic avian influenza viruses isolated from poultry in Pakistan 2006-2008.

Nine avian influenza viruses (AIV), H5N1 subtype, were isolated from dead poultry in the Karachi region of Pakistan from 2006 to 2008. The intravenous pathogenicity indices and HA protein cleavage sites of all nine viruses were consistent with highly pathogenic AIV. Based on phylogenetic analysis of the HA genes, these isolates belong to clade 2.

Left ventricular mass and functions in normotensive offspring of hypertensive parents: an echocardiographic study.

Objective: Published observations about cardiovascular alterations in normotensive individuals genetically predisposed to develop essential hypertension are conflicting. We tested the hypothesis that abnormalities in left ventricular mass and/or functions may be present in normotensive children of hypertensive parents.

Methods: One hundred normotensive offsprings (6 to 18 year age) of hypertensive parents (OHP) and an equal number of age- and sex-matched normotensive offsprings of normotensive parents (ONP) were studied with 2-dimensionally guided M-mode and Doppler echocardiography for left ventricular (LV) dimensions, mass, and systolic and diastolic functions.

Molecular characterization of Pakistani field isolates of infectious bursal disease virus.

The reverse transcriptase-polymerase chain reaction followed by restriction fragment length polymorphism (RT-PCR/RFLP) technique was used to identify and characterize Pakistani field isolates of infectious bursal disease virus (IBDV). These isolates have caused heavy losses to the poultry industry (mortality up to 60%) during the period between 1999 and 2005. Ten samples (five local isolates and five commercial vaccines) were examined for IBDV.

Etiological factors and clinical profile of adhesive capsulitis in patients seen at the rheumatology clinic of a tertiary care hospital in India.

Objective: This study was conducted to examine the clinical profile of patients with adhesive capsulitis (AC) and evaluate various possible etiological factors.

Methods: The study was conducted in the Department of Physical Medicine and Rehabilitation, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India. One hundred patients fulfilling the criteria for the diagnosis of AC were studied for the severity of shoulder pain and the range of shoulder movements.