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Metabolomic reprogramming plays a crucial role in the activation of several regulatory mechanisms including neuronal responses of the host. In the present study, alterations at physiological and biochemical levels were initially assessed to monitor the impact of the candidate pathogen Cronobacter sakazakii on the nematode host Caenorhabditis elegans. The abnormal behavioral responses were observed in infected worms in terms of hyperosmolarity and high viscous chemicals. The microscopic observations indicated reduction in egg laying and internal hatching of larvae in the host. An increased level of total reactive oxygen species and reduction in antioxidant agents such as glutathione and catalase were observed. These observations suggested the severe effect of C. sakazakii infection on C. elegans. To understand the small molecules which likely mediated neurotransmission, the whole metabolome of C. elegans during the infection of C. sakazakii was analyzed using liquid chromatography-mass spectrometry. A decrease in the quantity of methyl dopamine and palmitoyl dopamine and an increase in hydroxyl dopamine suggested that reduction in dopamine reuptake and dopamine neuronal stress. The disordered dopaminergic transmission during infection was confirmed using transgenic C. elegans by microscopic observation of Dat-1 protein expression. In addition, reduction in arachidonic acid and short-chain fatty acids revealed their effect on lipid droplet formation as well as neuronal damage. An increase in the quantity of stearoyl CoA underpinned the higher accumulation of lipid droplets in the host. On the other hand, an increased level of metabolites such as palmitoyl serotonin, citalopram N-oxide, and N-acyl palmitoyl serotonin revealed serotonin-mediated potential response for neuroprotection, cytotoxicity, and cellular damage. Based on the metabolomic data, the genes correspond to small molecules involved in biosynthesis and transportation of candidate neurotransmitters were validated through relative gene expression.

Sortase A, a transpeptidase enzyme is present in many Gram-positive bacteria and helps in the recruitment of the cell surface proteins. Over the last two decades, Sortase A has become an attractive tool for performing in vivo and in vitro ligations. Sortase A-mediated ligation has continuously been used for its specificity, robustness, and highly efficient nature. These properties make it a popular choice among protein engineers as well as researchers from different fields. In this review, we give an overview of Sortase A-mediated ligation of various molecules on the cell surfaces, which can have diverse applications in interdisciplinary fields.

The study of tropical diseases like leishmaniasis, a parasitic disease, has not received much attention even though it is the second-largest infectious disease after malaria. As per the WHO report, a total of 0.7–1.0 million new leishmaniasis cases, which are spread by 23 Leishmania species in more than 98 countries, are estimated with an alarming 26,000–65,000 death toll every year. Lack of potential vaccines along with the cost and toxicity of amphotericin B (AmB), the most common drug for the treatment of leishmaniasis, has raised the interest significantly for new formulations and drug delivery systems including nanoparticle-based delivery as anti-leishmanial agents. The size, shape, and high surface area to volume ratio of different NPs make them ideal for many biological applications. The delivery of drugs through liposome, polymeric, and solid-lipid NPs provides the advantage of high biocomatibilty of the carrier with reduced toxicity. Importantly, NP-based delivery has shown improved efficacy due to targeted delivery of the payload and synergistic action of NP and payload on the target. This review analyses the advantage of NP-based delivery over standard chemotherapy and natural product-based delivery system. The role of different physicochemical properties of a nanoscale delivery system is discussed. Further, different ways of nanoformulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite. The status of current nano-vaccines and the future potential of NP-based vaccine are elaborated here.

Severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) is a contagious pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. The pathogenesis and immunological responses of SARS-CoV-2 infection are poorly understood until now. Once a person gets infected by SARS-COV-2, both innate and adaptive immunity gets compromised, which further plays an important role in making the disease more severe. The host's innate immune system forms the first layer of defense for protection from viral infections and initiates activation of the adaptive immune system in order to give maximum protection. The respiratory tract maintains the balance of T cell, B cell pro- and anti-inflammatory responses in order to protect the tissue from damage and diseases. In this review, the current updates related to the involvement of the immune system in the antiviral defense against SARS-CoV-2 have been discussed. These novel insights within the immunological response in the respiratory tract would support the future development of vaccines and immunoregulatory therapy for SARS-CoV-2 infection.

Staphylococcus aureus is one of the most notorious pathogens and is frequently associated with nosocomial infections imposing serious risk to immune-compromised patients. This is in part due to its ability to colonize at the surface of indwelling medical devices and biofilm formation. Combating the biofilm formation with antibiotics has its own challenges like higher values of minimum inhibitory concentrations. Here, we describe a new approach to target biofilm formation by Gram positive bacteria. Sortase A is a transpeptidase enzyme which is responsible for tagging of around ∼22 cell surface proteins onto the outer surface. These proteins play a major role in the bacterial virulence. Sortase A recognizes its substrate through LPXTG motif. Here, we use this approach to install the synthetic peptide substrates onS. aureus. Sortase A substrate mimic, 6His-LPETG peptide was synthesized using solid phase peptide chemistry. Incorporation of the peptide on the cell surface was measured using ELISA. Effect of peptide incubation on Staphylococcus aureus biofilm was also studied. 71.1% biofilm inhibition was observed with 100 μM peptide while on silicon coated rubber latex catheter, 45.82% inhibition was observed. The present work demonstrates the inability of surface modified S. aureus to establish biofilm formation thereby presenting a novel method for attenuating its virulence.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has emerged into a global health and economic menace. Amidst the COVID-19 turmoil, recent failures/uncertain outcomes in clinical trials involving the anti-malarial (hydroxychloroquine), anti-viral (remdesivir) or the combination of anti-malarial/antibiotic (hydroxychloroquine/azithromycin) regimens have predisposed the physicians to distrust these "highly-touted" drugs for COVID-19. In this milieu, immunotherapy might be a credible modality to target or modify specific/non-specific immune responses that interfere with the survival of intracellular pathogens. This scientific review throws light on the epidemiology of COVID-19, its pathogenesis and the current clinical scenario of immunotherapeutics including convalescent plasma (CP), type-1 interferons (IFN-I) and human monoclonal antibodies (mAbs) to combat COVID-19. The treatment outcomes underscore that immunotherapy might be a reliable tool to assuage COVID-19-associated immunopathology. However, specific patient pool studies are warranted to ascertain the precise (re)purposing of immunotherapeutics for COVID-19.

Infection following injury is one of the major threats which causes huge economic burden in wound care management all over the world. Injury often results with poor healing when coupled by following infection. In contrast to this, we observed enhanced survival of wound infected worms compared to wounded worms in Caenorhabditis elegans wound model while infecting with Staphylococcus aureus. Hence, the study was intended to identify the mechanism for the enhanced survival of wound infected worms through LCMS/MS based high throughput proteomic analysis. Bioinformatics analyses of the identified protein players indicated differential enrichment of several pathways including MAPK signaling, oxidative phosphorylation and phosphatidylinositol signaling. Inhibition of oxidative phosphorylation and phosphatidylinositol signaling through chemical treatment showed complete reversal of the enhanced survival during wound infection nevertheless mutant of MAPK pathway did not reverse the same. Consequently, it was delineated that oxidative phosphorylation and phosphatidylinositol signaling are crucial for the survival. In this regard, elevated calcium signals and ROS including O- and H2O2 were observed in wounded and wound infected worms. Consequently, it was insinuated that presence of pathogen stress could have incited survival in wound infected worms with the aid of elevated ROS and calcium signals.

Objective: The present study aimed to develop and evaluate orally administrable dosage form containing bioactive flavonoids viz., Luteolin-7-O-β-D-Glucuronide (II), Kaempferol 3-O-[2-O-(6-O-feruloyl)-β-D-glucopyranosyl]-βD-galactopyranoside (III) from the bark of Givotia rottleriformis and Formononetin-7-O-β-D-glucoside (VI) from the leaves of Cassia tora. Methods: The formulation was developed and evaluated as per official compendia. The developed formulation was evaluated for antipsoriatic activity using rat UV ray photo dermatitis model and cytokine inhibition assay. Results: Evaluation parameters observed optimum range of formulations and the tablets were suitable for oral administration. The formulation exhibited antipsoriatic activity by good reduction in the thickness of epidermis, significant retention of the stratum granulosum and the absence of movement of neutrophils in UV-B induced psoriasis. In cytokine inhibition assay, the formulation showed remarkable inhibition of IL-17 and TNF- α, key cytokines involved in the pathogenesis of psoriasis at higher concentration. Conclusion: The study can be concluded that the developed formulation can be effective and safety as dietary supplements with health benefits to psoriatic patients.

Inflammatory conditions associated with kidney diseases are a global public health issue that requires efficient and safe therapies. Current treatment of renal inflammatory conditions using modern medicines has limitations such as undesired adverse effects, especially in long-term use. Combinations of herbs derived from historical medicinal practice such as Kampo (Japanese herbal formulation) and traditional Chinese medicines were found to synergistically elevate the therapeutic efficacy, and lowering the dose of specific herbal extracts could reduce the side effects if there were any. The clinical practice of traditional Kampo medicine is often followed in Japan for a range of health issues, including acute and chronic renal diseases. Owing to its well-known clinical tradition there has been a significant effort since 1995 devoted to evaluating the individual mechanistic properties of common Kampo formulas. In this chapter, the characteristics of Kampo medicine, especially in renal inflammatory diseases, are briefly reviewed. The pharmacological activity of important Kampo formulations, supported by either in vitro or animal studies, is presented. Reports on randomized clinical trials of traditional herbal medicines for kidney disease and required future directions are also discussed.

Objective: To synthesis chitosan reduced gold particle by using gymnemic acid isolated from Gymnema sylvestre leaves and to evaluate the antidiabetic activity against streptozocin and highfat diet treated rats. Methods: In this research paper, the synthesis gold particle by using gymnemic acid isolated from Gymnema sylvestre leaves with chitosan reducer. The synthesized AuNps were determined by UV–vis spectrum, high resolution transmission electron microscopy, X-ray diffraction, and Fourier transmission infrared spectroscopy analysis. The synthesized gymnemic acid coated chitosan reduced gold nanoparticles is subjected to evaluate its antidiabetic activity using high fat diet fed streptozotocin induced type 2 diabetes mellitus rats. Results: UV–vis spectrum showed a peak at 520 nm due to excitation of surface Plasmon vibrations. Fourier transmission infrared spectroscopy showed that nanoparticles were coated with plant secondary metabolites. HR-TEM and AFM images of synthesized AuNPS are spherical in shape and HR-TEM pictures evidently confirms the prepared AuNPS have the uniformed spherical shape with diameter of 14±3.69 nm in size respectively. The result of antidiabetic activity, chitosan reduced gold nano particles shows significant in both invitro and invivo models in high fat diet fed streptozotocin induced type 2 diabetes mellitus

D-Galactosamine (GalN)-induced liver injury is associated with reactive oxygen species and oxidative stress. In the present study, we evaluated the effect of alpha lipoic acid (ALA) supplementation on acute GalN-induced oxidative liver injury. Hepatotoxicity induced by single intraperitoneal injection of GalN (500 mg/kg body wt) was evident from increase in lipid peroxidation and serum marker enzymes (asparate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase). The decreased activities of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) as well as glutathione levels were the salient features observed in GalN-induced hepatotoxicity. Pretreatment with ALA (50 mg/kg body weight for 7 days) significantly precluded these changes and prevents the hepatic injury. Hence, this study clearly exemplified that ALA might be a suitable candidate against GalN-induced cellular abnormalities.

Azathioprine (AZA), one of the widely prescribed immunosuppressant drugs in organ transplantation and autoimmune diseases, could cause hepatotoxicity in the course of therapy. The current work was designed to assess the protective role of the dietary flavonoid, quercetin (QE), in oxidative hepatic damage induced by AZA. Adult male Wistar rats were divided into four treatment groups. Two groups were treated with single intraperitoneal injection of AZA (50 mg/kg body weight); one of these groups was pretreated with QE (50 mg/kg body weight) intraperitoneally once a day for 7 days. A vehicle treated control group and a QE control group were also included. Hepatotoxicity, evident from increased levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (GGT) in serum 24 h after AZA treatment, was significantly (p < 0.05) normalized by QE pretreatment. AZA administered rats displayed declined levels of endogenous antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)], along with elevated levels of malondialdehyde (MDA). However, pretreatment with QE significantly precluded lipid peroxidation and maintained the activities of antioxidant defenses at a near normal status. Besides, AZA induced oxidative stress and subsequent DNA damage was effectively manifested by QE, which was confirmed by agarose gel electrophoresis. These findings highlight the salubrious effect of QE as a hepatoprotectant in AZA-induced oxidative stress mediated hepatic injury.