MetaCompare 2.0: differential ranking of ecological and human health resistome risks.

While numerous environmental factors contribute to the spread of antibiotic resistance genes (ARGs), quantifying their relative contributions remains a fundamental challenge. Similarly, it is important to differentiate acute human health risks from environmental exposure, versus broader ecological risk of ARG evolution and spread across microbial taxa. Recent studies have proposed various methods for achieving such aims.

p-Coumaric acid protects against D-galactose induced neurotoxicity by attenuating neuroinflammation and apoptosis in mice brain.

D-galactose (D-gal) induced senescence in rodents is a widely used model for assessment of molecules affecting brain ageing. Chronic administration of D-gal causes neuroinflammation leading to cognitive deficit and memory impairment which represent Alzheimer's dementia. In present study, we investigated the neuroprotective effects of the natural phenol, p-Coumaric acid (PCA) and its underlying mechanism in the chronic D-gal treated mice.

In vitro and in vivo evaluation of a standardized Curcuma longa Linn formulation in cervical cancer.

Background: The anti-cancer activity of phytomolecules present in turmeric or haridra (Curcuma longa Linn) extracts against cancer has been described in various 'in vitro and in vivo' studies.

Objective: In the present study, in vitro and in vivo anti-cancer and chemo-preventive activity of a new standardized Supercritical Turmeric Oil Extract (SCTOE) NBFR-03 was evaluated in cervical cancer models.

Methods And Materials: In vitro cytotoxicity of this formulation was assessed at 10, 20, 40, and 80 μg/ml concentrations, in three cervical cancer cell lines (HeLa, SiHa, ME180) using Sulforhodamine B assay.

p-Coumaric acid mitigates lipopolysaccharide induced brain damage via alleviating oxidative stress, inflammation and apoptosis.

Objectives: Systemic administration of lipopolysaccharide induces neuroinflammation leading to cognitive deficit and memory impairment. Herein, we investigated the effects of p-Coumaric acid (PCA) in LPS induced neuroinflammation in mice. PCA is reported to possess free radicle scavenging and neuroprotective action.

Ruxolitinib, a JAK1/JAK2 selective inhibitor, ameliorates acute and chronic steroid-refractory GvHD mouse models.

Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation.  We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy in three different preclinical models of GvHD.  Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators of transcription target inhibition, significantly reduced alloreactive T-cell activation and infiltration in the lung and skin, leading to improved outcomes in two experimental models of steroid-refractory acute and chronic GvHD.

Hydrogen Sulfide Ameliorates Lipopolysaccharide-Induced Memory Impairment in Mice by Reducing Apoptosis, Oxidative, and Inflammatory Effects.

Hydrogen sulfide (HS) is reported to have a neuroprotective activity; however, the role of HS in neuroinflammation-induced neuronal damage is ambiguous. Here, we aimed to evaluate the underlying mechanisms for the neuroprotective effect of NaHS, a known HS donor, against lipopolysaccharide (LPS)-induced memory impairment (MI). All the treatments were administered for 28 days, and LPS (0.

Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.

Oxidative stress plays a pivotal part in the manifestation of neuroinflammation, which further leads to neurodegenerative diseases like Alzheimer's disease (AD). Systemic administration of lipopolysaccharide (LPS) induces neuroinflammation resulting in memory impairment (MI) and cognitive decline. In this study, we evaluated whether prophylactic administration of Rosmarinic acid (RA), a naturally occurring compound, exerts a neuroprotective effect in LPS-induced MI and cognitive decline.

Itacitinib (INCB039110), a JAK1 Inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-cell Therapy.

Purpose: T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown long-term relapse-free survival in patients with B-cell leukemia and lymphoma. However, cytokine release syndrome (CRS) represents a serious, potentially life-threatening side effect often associated with CAR T-cell therapy.

Insulin resistance: a connecting link between Alzheimer's disease and metabolic disorder.

Recent evidence suggests that Alzheimer's disease (AD) is closely linked with insulin resistance, as seen in type 2 diabetes mellitus (T2DM). Insulin signaling is impaired in AD brains due to insulin resistance, ultimately resulting in the formation of neurofibrillary tangles (NFTs). AD and T2DM are connected at molecular, clinical, and epidemiological levels making it imperative to understand the contribution of T2DM, and other metabolic disorders, to AD pathogenesis.

Preclinical characterization of itacitinib (INCB039110), a novel selective inhibitor of JAK1, for the treatment of inflammatory diseases.

Pharmacological modulation of the Janus kinase (JAK) family has achieved clinically meaningful therapeutic outcomes for the treatment of inflammatory and hematopoietic diseases. Several JAK1 selective compounds are being investigated clinically to determine their anti-inflammatory potential. We used recombinant enzymes and primary human lymphocytes to assess the JAK1 specificity of itacitinib (INCB039110) and study inhibition of signal transducers and activators of transcription (STAT) signaling.

Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment.

Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death.

Chrysin mitigated obesity by regulating energy intake and expenditure in rats.

Background And Aim: Chrysin is a flavonoid found in plant extracts from species, honey and propolis. It has demonstrated anti-adipogenic activity but there are no studies substantiating the anti-obesity activity of chrysin .

Experimental Procedure: The pancreatic lipase (PL) inhibitory potential of chrysin was determined by preliminary screening and further confirmed by PL inhibitory assay and oral fat tolerance test (OFTT).

Chrysin ameliorates nonalcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of the metabolic syndrome. It begins with the accumulation of fat in the liver (simple steatosis), which if untreated can progress to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Chrysin is a flavonoid present in bee propolis and many other plants.

Plumbagin reduces obesity and nonalcoholic fatty liver disease induced by fructose in rats through regulation of lipid metabolism, inflammation and oxidative stress.

Background: Chronic consumption of fructose causes obesity and nonalcoholic fatty liver disease (NAFLD). Currently available therapies have limitations; hence there is a need to screen new molecules. Plumbagin is a naphthoquinone present in the roots of Plumbago species which has hypolipidemic and hepatoprotective activities.

Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor.

Background: Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy.

Objective: In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation.

Plumbagin exerts antiobesity effects through inhibition of pancreatic lipase and adipocyte differentiation.

Plumbagin is a naphthoquinone found in the roots of Plumbago zeylanica. Here, we report an investigation to evaluate its antiobesity activity. The preliminary binding affinity of plumbagin to human pancreatic lipase (PL) was determined using molecular docking simulation.

Punica granatum improves renal function in gentamicin-induced nephropathy in rats via attenuation of oxidative stress.

Background: Gentamicin is widely used as an antibiotic for the treatment of gram negative infections. Evidences indicates that oxidative stress is involved in gentamicin-induced nephrotoxicity. In Ayurvedic medicine, Punica granatum Linn.

In vitro antiglycating effect and in vivo neuroprotective activity of Trigonelline in d-galactose induced cognitive impairment.

Background: Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles (NFTs) and cognitive impairment. Literature cites the role of advanced glycation end products (AGEs) in AD due to increased cytotoxicity via oxidative stress. d-galactose (d-gal) induced amnesia stimulates Aβ overproduction via increased oxidative stress and AGEs.

Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice.

Neuroinflammation is said to play a pivotal role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Trigonelline (TRG) is a naturally occurring alkaloid, commonly isolated from fenugreek and coffee beans. In the present study, we investigated whether TRG exerts neuroprotective action against LPS mediated cognitive impairment.

Design, synthesis and biological evaluation of novel pyrazolochalcones as potential modulators of PI3K/Akt/mTOR pathway and inducers of apoptosis in breast cancer cells.

Cancer has been established as the "Emperor of all maladies". In recent years, medicinal chemistry has focused on identifying novel anti-cancer compounds; though discovery of these compounds appears to be a herculean task. In present study, we synthesized forty pyrazolochalcone conjugates and explored their cytotoxic activity against a panel of sixty cancer cell lines.

Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Linn. leaves extract.

With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of leaves (MPGL) in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. , due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy.

Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway.

Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders.

Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson's disease.

Curcumin, a natural polyphenolic compound extracted from rhizomes of Curcuma longa (turmeric), a plant in the ginger family (Zingiberaceae) has been used worldwide and extensively in Southeast Asia. Curcumin exhibited numerous biological and pharmacological activities including potent antioxidant, cardiovascular disease, anticancer, anti-inflammatory effects and neurodegenerative disorders in cell cultures and animal models. Hence, the present study was designed in order to explore the possible neuroprotective role of curcumin against rotenone induced cognitive impairment, oxidative and mitochondrial dysfunction in mice.

Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators.

Experimental and clinical evidence indicates that pro-inflammatory cytokines, oxidative stress and brain-derived neurotrophic factor (BDNF) signalling mechanisms play a role in the pathophysiology of depression. Agmatine is a neurotransmitter and/or neuromodulator that has emerged as a potential agent to manage diverse central nervous system disorders. Agmatine has been shown to exert antidepressant-like effect.

Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion.

We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a consequence of impaired production of nucleotides needed for DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all four nucleotide triphosphates, whereas inhibition of the protein kinase AKT is less effective than inhibition of PI3K in suppressing nucleotide synthesis and inducing DNA damage.