The Role of Complement Component C3 in Protection Against Pseudomonas Pneumonia-Induced Lung Injury.

The complement system is a family of proteins that facilitate immune resistance by attacking microbes to decrease pathogen burden. As a result, deficiencies of certain complement proteins result in recurrent bacterial infections, and can also result in acute lung injury (ALI). We and others have shown that C3 is present in both immune and nonimmune cells, and modulates cellular functions such as metabolism, differentiation, cytokine production, and survival. Although the emerging roles of the complement system have implications for host responses to ALI, key questions remain vis-a-vis the lung epithelium. In this review, we summarize our recent article in which we reported that during Pseudomonas aeruginosa-induced ALI, lung epithelial cell-derived C3 operates independent of liver-derived C3. Specifically, we report the use of a combination of human cell culture systems and global as well as conditional knockout mouse models to demonstrate the centrality of lung epithelial cell-derived C3. We also summarize recent articles that have interrogated the role of intracellular and/or locally derived C3 in host defense. We propose that C3 is a highly attractive candidate for enhancing tissue resilience in lung injury as it facilitates the survival and function of the lung epithelium, a key cell type that promotes barrier function.

Theranostics: a multifaceted approach utilizing nano-biomaterials.

Biomaterials play a vital role in targeting therapeutics. Over the years, several biomaterials have gained wide attention in the treatment and diagnosis of diseases. Scientists are trying to make more personalized treatments for different diseases, as well as discovering novel single agents that can be used for prognosis, medication administration, and keeping track of how a treatment works. Theranostics based on nano-biomaterials have higher sensitivity and specificity for disease management than conventional techniques. This review provides a concise overview of various biomaterials, including carbon-based materials like fullerenes, graphene, carbon nanotubes (CNTs), and carbon nanofibers, and their involvement in theranostics of different diseases. In addition, the involvement of imaging techniques for theranostics applications was overviewed. Theranostics is an emerging strategy that has great potential for enhancing the accuracy and efficacy of medicinal interventions. Despite the presence of obstacles such as disease heterogeneity, toxicity, reproducibility, uniformity, upscaling production, and regulatory hurdles, the field of medical research and development has great promise due to its ability to provide patients with personalised care, facilitate early identification, and enable focused treatment.

Beneficial effect of 5-HT1b/1d agonist on Parkinson's disease by modulating glutamate and reducing deposition of α-synuclein.

The given investigation examined the neuroprotection role of 5-HT1b/1d agonist in reserpine induced Parkinson's disease (PD) in male Wistar rats. PD was induced in rats by reserpine at 5 mg/kg ip for 3 days and thereafter the rats were provided with the following treatments for 4 days, zolmitriptan (ZLM) group (30 mg/kg ip); STD group (levodopa + carbidopa, 200 + 5 mg/kg ip); ZLM + GA group (zolmitriptan, 30 mg/kg ip and glutamic acid, 1.5 mg/kg); ZLM + DX group (zolmitriptan, 30 mg/kg ip and dextromethorphan, 20 mg/kg ip). All the groups were then assessed for cognitive and motor functions at the end of the protocol. Moreover, oxidative stress parameters and histopathological changes were observed in rats of all treatment groups. Deposition of α-synuclein in the brain tissue was observed by silver staining. Data of this investigation revealed that motor and cognitive functions were improved in the ZLM-treated group compared with the negative control group, which was observed to be reversed in ZLM + GA group. Treatment with ZLM ameliorated oxidative stress and histopathological changes in the brain tissue of PD rats. Further, ZLM reduced the deposition of α-synuclein in PD rats, which reversed in ZLM + GA-treated group. This study concludes by stating that 5-HT1b/1d agonist can prevent neurodegeneration and reduce oxidative stress in PD rats. The probable underlying mechanism of such an effect of 5-HT1b/1d agonist could be by regulating the deposition of α-synuclein and reducing the expression of NMDA receptor.

An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes.

Diabetes or diabetes mellitus is a complex or polygenic disorder, which is characterized by increased levels of glucose (hyperglycemia) and deficiency in insulin secretion or resistance to insulin over an elongated period in the liver and peripheral tissues. Thiazolidine-2,4-dione (TZD) is a privileged scaffold and an outstanding heterocyclic moiety in the field of drug discovery, which provides various opportunities in exploring this moiety as an antidiabetic agent. In the past few years, various novel synthetic approaches had been undertaken to synthesize different derivatives to explore them as more potent antidiabetic agents with devoid of side effects (i.e., edema, weight gain, and bladder cancer) of clinically used TZD (pioglitazone and rosiglitazone). In this review, an effort has been made to summarize the up to date research work of various synthetic strategies for TZD derivatives as well as their biological significance and clinical studies of TZDs in combination with other category as antidiabetic agents. This review also highlights the structure-activity relationships and the molecular docking studies to convey the interaction of various synthesized novel derivatives with its receptor site.

Antileishmanial Activity of Pyrazolopyridine Derivatives and Their Potential as an Adjunct Therapy with Miltefosine.

A series of pyrazolo(dihydro)pyridines was synthesized and evaluated for antileishmanial efficacy against experimental visceral leishmaniasis (VL). Among all compounds, 6d and 6j exhibited better activity than miltefosine against intracellular amastigotes. Compound 6j (50 mg/kg/day) was further studied against Leishmania donovani/BALB/c mice via the intraperitoneal route for 5 days and displayed >91 and >93% clearance of splenic and liver parasitic burden, respectively. Combination treatment of 6j with a subcurative dose of miltefosine (5 mg/kg) in BALB/c mice almost completely ameliorated the disease (>97% inhibition) by augmenting nitric oxide generation and shifting the immune response toward Th1. Furthermore, investigating the effect of 6j on Leishmania promastigotes revealed that it induced molecular events, such as a loss in mitochondrial membrane potential, externalization of phosphatidylserine, and DNA fragmentation, that ultimately resulted in the programmed cell death of the parasite. These results along with pharmacokinetic studies suggest that 6j could be a promising lead for treating VL as an adjunct therapy with miltefosine.

H2O2/DMSO-Promoted Regioselective Synthesis of 3,3'-Bisimidazopyridinylmethanes via Intermolecular Oxidative C(sp(2))-H Bond Activation of Imidazoheterocycles.

In the past decade, metal-free approaches for C-C bond formation have attracted a great deal of attention due to their ease of use and low cost. This report represents a novel and metal-free synthesis of 3,3'-bisimidazopyridinylmethanes via intermolecular oxidative C(sp(2))-H bond functionalization of imidazo[1,2-a]pyridines with dimethyl sulfoxide as the carbon synthon (CH2) using H2O2 as a mild oxidant under air. A library of 3,3'-bis(2-arylimidazo[1,2-a]pyridin-3-yl)methanes has been achieved in good to excellent yields. The present methodology has been successfully applied to imidazo[2,1-b]thiazoles and imidazo[2,1-b]benzothiazoles. Furthermore, the current approach was also extended for the synthesis of unsymmetrical 3,3'-bisimidazopyridinylmethanes under optimized reaction conditions. A mechanistic pathway is proposed on the basis of experiments with radical scavengers and DMSO-d6 and ESI-MS observations.

Substrate Controlled Synthesis of Benzisoxazole and Benzisothiazole Derivatives via PhI(OAc)2-Mediated Oxidation Followed by Intramolecular Oxidative O-N/S-N Bond Formation.

A phenyliodine(III) diacetate (PIDA)-mediated, highly efficient and tandem approach for the synthesis of aryldiazenylisoxazolo(isothiazolo)arenes from simple 2-amino-N'-arylbenzohydrazides has been developed. The reaction proceeds via formation of (E)-(2-aminoaryl)(aryldiazenyl)methanone as the key intermediate, followed by intramolecular oxidative O-N/S-N bond formation in one pot at room temperature. The quiet different reactivity of the substrate is due to the formation of a diazo intermediate which encounters a nucleophilic attack by carbonyl oxygen on the electrophilic amine to produce isoxazole products, as compared to the previous reportsa,b,4 in which an N-acylnitrenium ion intermediate is intramolecularly trapped by an amine group.