Background: Obesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. The role of AMP-activated protein kinase in adipocyte differentiation is not completely understood, therefore, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK) on adipocyte differentiation in 3T3L1 cells and in a mouse D iet i nduced o besity (DIO) model. Methods: To examine the effect of AICAR on adipocyte differentiation in 3T3L1 cells and in a mouse D iet i nduced o besity (DIO) model, 3T3L1 cells were differentiatied in the presence or absence of different concentration of AICAR and neutral lipid content and expression of various adipocyte-specific transcription factors were examined. In vivo study, treated and untreated mice with AICAR (0.1–0.5 mg/g body weight) were fed high-fat diet (60% kcal% fat) to induce DIO and several parameters were studied. Results: AICAR blocked adipogenic conversion in 3T3L1 cells along with significant decrease in the neutral lipid content by downregulating several adipocyte-specific transcription factors including peroxisome proliferators-activated receptor γ (PPARγ), C/EBPα and ADD1/SREBP1, which are critical for adipogenesis in vitro. Moreover, intraperitoneal administration of AICAR (0.5 mg g/body weight) to mice fed with high-fat diet (60% kcal% fat) to induce DIO, significantly blocked the body weight gain and total content of epididymal fat in these mice over a period of 6 weeks. AICAR treatment also restored normal adipokine levels and resulted in significant improvement in glucose tolerance and insulin sensitivity. The reduction in adipose tissue content in AICAR treated DIO mice was due to reduction in lipid accumulation in the pre-existing adipocytes. However, no change was observed in the expression of PPARγ, C/EBPα and ADD1/SREBP1 transcription factors in vivo though PGC1α expression was significantly induced. Conclusion: This study suggests that AICAR inhibits adipocyte differentiation via downregulation of expression of adipogenic factors in vitro and reduces adipose tissue content in DIO mice by activating expression of PGC1α without inhibiting adipocyte-specific transcription factors in DIO mice.

Scavenger receptors belong to a superfamily of proteins that are structurally heterogeneous and encompass the miscellaneous group of transmembrane proteins and soluble secretory extracellular domain. They are functionally diverse as they are involved in various disorders and biological pathways and their major function in innate immunity and homeostasis. Numerous scavenger receptors have been discovered so far and are apportioned in various classes (A-L). Scavenger receptors are documented as pattern recognition receptors and known to act in coordination with other co-receptors such as Toll-like receptors in generating the immune responses against a repertoire of ligands such as microbial pathogens, non-self, intracellular and modified self-molecules through various diverse mechanisms like adhesion, endocytosis and phagocytosis etc. Unlike, most of the scavenger receptors discussed below have both membrane and soluble forms that participate in scavenging; the role of a potential scavenging receptor Angiotensin-Converting Enzyme-2 has also been discussed whereby only its soluble form might participate in preventing the pathogen entry and replication, unlike its membrane-bound form. This review majorly gives an insight on the functional aspect of scavenger receptors in host defence and describes their mode of action extensively in various immune pathways involved with each receptor type.

Background: The present study was conducted to evaluate the in vitro and in vivo antioxidant properties of aqueous extract of Podophyllum hexandrum. The antioxidant potential of the plant extract under in vitro situations was evaluated by using two separate methods, inhibition of superoxide radical and hydrogen peroxide radical. Carbon tetrachloride (CCl₄) is a well known toxicant and exposure to this chemical is known to induce oxidative stress and causes tissue damage by the formation of free radicals. Methods: 36 albino rats were divided into six groups of 6 animals each, all animals were allowed food and water ad libitum. Group I (control) was given olive oil, while the rest groups were injected intraperitoneally with a single dose of CCl₄ (1 ml/kg) as a 50% (v/v) solution in olive oil. Group II received CCl₄ only. Group III animals received vitamin E at a concentration of 50 mg/kg body weight and animals of groups IV, V and VI were given extract of Podophyllum hexandrum at concentration dose of 20, 30 and 50 mg/kg body weight. Antioxidant status in both kidney and lung tissues were estimated by determining the activities of antioxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and superoxide dismutase (SOD); as well as by determining the levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). In addition, superoxide and hydrogen peroxide radical scavenging activity of the extract was also determined. Results: Results showed that the extract possessed strong superoxide and hydrogen peroxide radical scavenging activity comparable to that of known antioxidant butylated hydroxy toluene (BHT). Our results also showed that CCl₄ caused a marked increase in TBARS levels whereas GSH, SOD, GR, GPX and GST levels were decreased in kidney and lung tissue homogenates of CCl₄ treated rats. Aqueous extract of Podophyllum hexandrum successfully prevented the alterations of these effects in the experimental animals. Conclusion: Our study demonstrated that the aqueous extract of Podophyllum hexandrum could protect the kidney and lung tissue against CCl₄ induced oxidative stress probably by increasing antioxidant defense activities.

This study delineates the molecular mechanism underlying psychosine‐induced oligodendroglial cell death. An immortalized human oligodendroglial cell line, MO3.13, was treated with exogenous psychosine (β‐galactosylsphingosine), a toxic metabolite that accumulates in the tissues of patients with Krabbe's disease. The mode of cell death induced by psychosine was found to be apoptotic, as revealed by different apoptotic markers viz., TUNEL, DNA fragmentation and caspase cleavage/activation. The action of psychosine was redox sensitive, as measured by changes in mitochondrial membrane potential (ψΔ), and this effect of psychosine could be reversed by pre‐treatment with the antioxidant molecules N‐acetyl‐l‐cysteine or pro‐cysteine. Psychosine directly affects the mitochondria as revealed by the activation of caspase 9 but not caspase 8. Up‐regulation of the c‐jun/c‐jun N‐terminal kinase pathway by psychosine leads to the induction of AP‐1 and, at the same time, psychosine also down‐regulates the lipopolysaccharide‐induced NF‐κB transactivation. These observations indicate that the mechanism of action of psychosine is, through the up‐regulation of AP‐1, a pro‐apoptotic pathway as well as, through the down‐regulation of the NF‐κB pathway, an antiapoptotic pathway.

The only part of an antigen (a protein molecule found on the surface of a pathogen) that is composed of epitopes specific to T and B cells is recognized by the human immune system (HIS). Identification of epitopes is considered critical for designing an epitope-based peptide vaccine (EBPV). Although there are a number of vaccine types, EBPVs have received less attention thus far. It is important to mention that EBPVs have a great deal of untapped potential for boosting vaccination safety—they are less expensive and take a short time to produce. Thus, in order to quickly contain global pandemics such as the ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as well as epidemics and endemics, EBPVs are considered promising vaccine types. The high mutation rate of SARS-CoV-2 has posed a great challenge to public health worldwide because either the composition of existing vaccines has to be changed or a new vaccine has to be developed to protect against its different variants. In such scenarios, time being the critical factor, EBPVs can be a promising alternative. To design an effective and viable EBPV against different strains of a pathogen, it is important to identify the putative T- and B-cell epitopes. Using the wet-lab experimental approach to identify these epitopes is time-consuming and costly because the experimental screening of a vast number of potential epitope candidates is required. Fortunately, various available machine learning (ML)-based prediction methods have reduced the burden related to the epitope mapping process by decreasing the potential epitope candidate list for experimental trials. Moreover, these methods are also cost-effective, scalable, and fast. This paper presents a systematic review of various state-of-the-art and relevant ML-based methods and tools for predicting T- and B-cell epitopes. Special emphasis is placed on highlighting and analyzing various models for predicting epitopes of SARS-CoV-2, the causative agent of COVID-19. Based on the various methods and tools discussed, future research directions for epitope prediction are presented.