Current Research in Pharmacology and Drug Discovery最新文献

The 2-((4-(chloromethyl)benzoyl)oxy)benzoic acid (4CH₂Cl) is a potential analgesic compound derived from salicylic acid and 4-chloromethyl benzoyl chloride. Characterization required 4CH₂Cl for the formulation of tablet dosage forms. This study aims investigate the effect of SSG, PVP-K30, and the combination of SSG*PVP K-30 on the formulation of 4CH₂Cl tablets. Additionally, this study aimed to obtain the optimum 4CH₂Cl tablet composition. The experiment followed the two-factor simplex lattice design and direct compression method. The analgesic activity of 4CH₂Cl in the optimal tablet was investigated using the hot-plate methods. The ANOVA of linear models is acceptable and the polynomial coefficients of quadratic models are similar to those of linear models. The coefficient of the linear model shows that SSG and PVP K-30 increase the Carr index (16.26; 20.61), Hausner ratio (1.19; 1.29), hardness (4.19; 9.39), friability (0.48; 0.67), disintegration time (0.34; 7.50), and drug release (85.29; 97.69). The coefficient of the quadratic model shows that SSG*PVP K-30 increased the Carr index (1.90), Hausner ratio (0.04), hardness (1.88), friability (0.06), and drug release (4.56), and decreased disintegration time (−0.30). SSG and PVP K-30 increased Carr index, Hausner ratio, hardness, friability, disintegration time, and drug release. The combination of SSG*PVP K-30 has the same effect, except that the disintegration time decreased. The optimum tablet formula is 4CH₂Cl (300 mg), Ne (75 mg), SSG (33.60 mg), PVP K-30 (22.40 mg), MCC (40 mg), and SDL (up to 800 mg). 4CH₂Cl tablets can be a candidate and choice for new analgesic drugs in the future.

Ischemia as the most common type of stroke is the main cause of death and disability in the world. However, there are few therapeutic approaches to treat ischemic stroke. The common approach to the treatment of ischemia includes surgery-cum-chemical drugs. Surgery and chemical drugs are used to remove blood clots to prevent the deterioration of the nervous system. Given the surgical hazards and the challenges associated with chemical drugs, these cannot be considered safe approaches to the treatment of brain ischemia. Besides surgery-cum-chemical drugs, different types of stem cells including mesenchymal stem cells and neurological stem cells have been considered to treat ischemic stroke. Therapeutic approaches utilizing stem cells to treat strokes are promising because of their neuroprotective and regenerative benefits. However, the mechanisms by which the transplanted stem cells perform their precisely actions are unknown. The purpose of this study is to critically review stem cell-based therapeutic approaches for ischemia along with related challenges.

Cholestasis is a hepatobiliary condition that manifests as acute or chronic and results from disruptions in the bile flow, formation, or secretion processes. The Farnesoid X receptor (FXR) is a vital target for the therapy of cholestasis since it regulates BA homeostasis. Despite the discovery of multiple active FXR agonists, there are still no effective treatments for cholestasis. Papaverine is identified as an FXR agonist.This study investigates papaverine's efficacy and probable mechanism in protecting against alpha naphthylisothiocyanate (ANIT) induced cholestasis. Thirty male albino rats were divided into three groups, each with ten rats. Group I (control) rats were administered 1 mL/kg corn oil 48 h before sacrifice; group II rats were orally administered 100 mg/kg ANIT. Group III received a 200 mg/kg dosage of papaverine over seven consecutive days. A single dose of ANIT at a concentration of 100 mg/kg was orally administered on the fifth day; group II and III animals were euthanized 48 h after inducing cholestasis, and serum concentrations of liver function tests and total bile acid (TBA) were measured. Besides measuring the inflammatory mediator's tumor necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1β), antioxidant markers such as superoxide dismutase (SOD) and glutathione (GSH) were also assessed. The findings indicated the enhancement in the liver function test and total bile acids, as well as in liver histology; papaverine significantly lowered TNF-α and IL-1β while SOD and GSH significantly increased. Additionally, papaverine upregulates Fxr gene expression, bile salt export pump (Besp), small heterodimer partner (shp), hepatocyte nuclear factor 1α (Hnfα), nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase (Ho-1), NAD(P)H quinone oxidoreductase 1 (Nqo1). Furthermore, papaverine increased protein expressions of Sirtuin1.

(SIRT 1), FXR, HO-1, and BSEP levels in the rats' livers. The protective effects of papaverine may be attributed to the activation of FXR signaling pathways. These findings revealed that papaverine protects against ANIT-induced Cholestasis.

GERD is a very familiar diagnosis among health care providers due to its massive spread, and its symptoms can affect the quality of life for a respectable slice of its patients. Therefore, what can only be described as a logical consequence, a pursuit of a treatment that can both relieve symptoms and have minimal side effects is still ongoing to cover the large demographic affected by GERD. In the following review, analysis will be made of GERD, including possible regulatory activity, of certain drugs to the already discussed pathways involved in GERD patients.

Nucleolar stress induced by stressors like hypoxia, UV irradiation, and heat shock downregulates ribosomal RNA transcription, thereby impairing protein synthesis capacity and potentially contributing to cell senescence and various human diseases such as neurodegenerative disorders and cancer. Live-cell imaging of the nucleolus may be a feasible strategy for investigating nucleolar stress, but currently available nucleolar stains are limited for this application. In this study using mouse hippocampal HT22 cells, we demonstrate that thioflavin T (ThT), a benzothiazole dye that binds RNA with high affinity, is useful for nucleolar imaging in cells where RNAs predominate over protein aggregates. Nucleoli were stained with high intensity simply by adding ThT to the cell culture medium, making it suitable for use even in damaged cells. Further, ThT staining overlapped with specific nucleolar stains in both live and fixed cells, but did not overlap with markers for mitochondria, lysosomes, endoplasmic reticulum, and double-stranded DNA. Ferroptosis, an iron-dependent nonapoptotic cell death pathway characterized by lipid peroxide accumulation, reduced the number of ThT-positive puncta while endoplasmic reticulum stress did not. These findings suggest that ferroptosis is associated with oxidative damage to nucleolar RNA molecules and ensuing loss of nucleolar function.

The part of sexuality in pharmacology research was not acknowledged, and it was not thought-out to be a determinant that could impact strength and disease. For decades research has mainly contained male, women and animals, leading to a lack of news about syndromes in females. Still, it is critical to guarantee equal likeness so that determine the security, influence, and resistance of healing agents for all individuals. The underrepresentation of female models in preclinical studies over various decades has surpassed to disparities in the understanding, disease, and treatment of ailments 'tween genders. The closeness of sexuality bias has happened recognized as a contributing determinant to the restricted interpretation and replicability of preclinical research. Many demands operation have stressed the significance of including sexuality as a organic changeable, and this view is acquire growing support. Regardless of important progress in incorporating more female models into preclinical studies, differences prevail contemporary. The current review focuses on the part of sexuality and common in biomedical research and, therefore, their potential function in pharmacology and analyze the potential risks guide.

Cancer continues to increase global morbidity and mortality rates. Despite substantial progress in the development of various chemically synthesized anti-cancer drugs, the poor prognosis of the disease still remains a big challenge. The most common drawback of conventional cancer therapies is the emergence of drug resistance eventually leading to the discontinuation of chemotherapy. Moreover, advanced target-specific therapies including immunotherapy and stem cell therapy are expensive enough and are unaffordable for most patients in poorer nations. Therefore, alternative and cheaper therapeutic strategies are needed to complement the current cancer treatment approaches. Phytochemicals are bioactive compounds produced naturally by plants and have great potential in human health and disease. These compounds possess antiproliferative, anti-oxidant, and immunomodulatory properties. Among the phytochemicals, flavonoids are very effective in treating a wide range of diseases from cardiovascular diseases and immunological disorders to cancer. They scavenge reactive oxygen species (ROS), inhibit cancer metastasis, modulate the immune system and induce apoptotic or autophagic cell death in cancers. This review will discuss the potential of various phytochemicals particularly flavonoids in attempts to target various cancers.

The significance of mesenchymal stem cells (MSCs) for tissue repair and regeneration is widely recognized. The pleiotropic nature of MSCs is demonstrated by their potential for proliferation and differentiation, and paracrine secretions, thereby making them ideal candidates for cell replacement therapy. Tissue resident MSCs are engaged in homeostasis under normal wear and tear. However, stem cell therapy may be applicable if damage cannot be repaired by normal homeostatic mechanisms. The safety of MSCs has been clearly established in clinical trials but their efficacy remains questionable. The efficacy of MSCs depends on several factors, such as their viability, functional status in terms of secretome secretions, and the in-vivo scenario after transplantation. The performance of MSCs is regulated by their micro-environmental conditions and cues. The so-called MSC niche comprises physical, chemical, and biological components, which play key roles in determining the fate of MSCs. MSCs scaled up for transplantation purposes comprise a disorganized mass of cells, which needs to be directed to perform the required function. Thus, MSCs need to be directed toward an expected target activity in human patients. This review focuses on the various methods that can be used to guide stem cells for cutaneous repair.

Soil-Transmitted Helminthiasis (STH) is one of the most widespread Neglected Tropical Diseases (NTDs), and almost 1.5 billion of the global population is affected, mostly in the indigent, countryside sectors of tropics/subtropics. STH, commonly caused by various nematodes, adversely affects the hosts’ growth, cognatic development, and immunity. Albendazole is most commonly used against STH (Soil-Transmitted Helminths) but resistance has already been reported in different countries. To date, no effective vaccine is present against STH. miRNAs are a unique class of small non-coding RNA, regulating various biological activities indulging host immune responses in host-pathogen interaction of STH. Dysregulation of miRNAs are being considered as one of the most important aspect of host-parasite interactions. Thus, it is the prime importance to identify and characterize parasite-specific as well as host-derived miRNAs to understand the STH infection at the molecular level. Systematic bibliometric analysis reveals a huge knowledge gap in understanding the disease by using both host and parasitic miRNAs as a potential biomarker. In this study, we addressed the present status of the STH prevalence, and therapy under the light of miRNAs. This would further help in designing new inhibitors and therapeutic strategies to control STH.