Current pharmaceutical biotechnology最新文献

The incidence of Coronavirus Disease 2019 (COVID-19) has increased dramatically in recent years, affecting millions of people worldwide. The primary cause of morbidity and mortality in COVID-19 patients is respiratory illness. However, the disease can also significantly impact the cardiovascular system. SARS-CoV-2, the virus responsible for COVID-19, enters cells using the angiotensin-converting enzyme 2 (ACE-2) receptor. ACE-2 is a component of the renin-angiotensin system (RAS) and plays a crucial role in regulating various pathological processes. The interaction of the virus with ACE-2 in the myocardium can lead to direct heart damage. Several mechanisms may contribute to myocardial damage in COVID-19 patients, including systemic inflammation, myocardial interstitial fibrosis, interferon-mediated immune response, exaggerated cytokine response, T-cell-mediated damage, coronary plaque instability, and hypoxia. There has been concern that ACE inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression. However, it may be advisable to continue medications for patients with underlying cardiovascular disorders. The precise mechanisms of cardiomyocyte injury in COVID-19 are not fully understood, but necroptosis appears to play a significant role. Current treatments for cardiac damage in COVID-19 patients include IL-6 blockers and antiplatelet therapy. Ponatinib, a small molecule tyrosine kinase inhibitor designed using computational and structural approaches, has shown the potential to affect cell death through its impact on tyrosine kinase activity. By reviewing studies related to ponatinib's effects on necroptosis and cell death, we propose a novel approach to potentially reduce the cardiotoxic effects of COVID-19 on cardiomyocytes. Further research is needed to fully elucidate the mechanisms of cardiac injury in COVID-19 and to develop targeted therapies to protect the heart from the devastating effects of this disease.

Type 2 diabetes mellitus is a serious metabolic disease having a high growth rate and becoming a global threat. An unhealthy lifestyle, food intake, and genetic susceptibility are the major factors responsible for this metabolic disorder. This disease results in hyperlipidemia, hyperglycemia, glucose intolerance, restricted insulin synthesis, and insulin resistance. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising approach to diabetes focuses on gut microflora and their associated metabolites. Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology. This study explores the dysbiosis in the human gut microflora in Type 2 Diabetes Mellitus and how the gut microbiota influences metabolites related to T2DM. It also sheds light on early identification and targeted intervention for this. Understanding these mechanisms could potentially lead to more effective strategies for managing and preventing T2DM. The findings of our literature study are that gut microbiota can serve as biomarkers for early disease detection. Finally, we also highlight gut microecological therapeutic strategies focused on shaping the gut flora to emphasize the improvement of T2DM progression.

Background: The relationship between uterine fibroids and keloid/hypertrophic scars has been contradictory. Our research employs a bidirectional Mendelian Randomization (MR) approach to establish a clearer understanding of this potential causal link.

Objective: This study aimed to determine the effect of uterine fibroids on keloid/hypertrophic scars and the effect of keloid/hypertrophic scars on uterine fibroids.

Purpose: We aimed to demonstrate the relationship between uterine fibroids and keloid/ hypertrophic scars.

Method: Our bidirectional MR study utilized summarized data from genome-wide association studies (GWAS) focused on European populations. Our primary tool for establishing causality was the Inverse-Variance Weighted (IVW) method. To reinforce the IVW findings, we also applied four alternative MR methods: MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median.

Result: The IVW method indicated a significant causal link, with uterine fibroids greatly raising the likelihood of developing keloids (Odds Ratio [OR] = 1.202, 95% Confidence Interval [CI]: 1.045-1.381; P=0.010) and hypertrophic scars (OR = 1.256, 95% CI: 1.039-1.519; P=0.018). Parallel results were observed with the MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median methods. Sensitivity analyses indicated robustness in these findings, with no evidence of heterogeneity or horizontal pleiotropy. Conversely, the reverse MR analysis did not demonstrate an increased risk of uterine fibroids due to keloids or hypertrophic scars.

Conclusion: This study elucidates a significant causal effect of uterine fibroids on the development of keloid and hypertrophic scars, offering valuable insights into their pathogenesis and potential therapeutic targets.

Proteases, a group of hydrolytic enzymes catalyzing the hydrolysis of peptide bonds, play pivotal roles in various physiological processes and have emerged as key contributors to the pathogenesis of diverse diseases. This work provides an insight into the impact of protease activity on different disease contexts, highlighting their involvement in cancer, inflammatory disorders, cardiovascular diseases, infectious diseases, and neurodegenerative conditions. In cancer, proteases facilitate tumor growth, invasion, and metastasis, while in inflammatory diseases, dysregulated protease activity exacerbates tissue damage and inflammation. Cardiovascular diseases involve proteases in extracellular matrix remodeling, affecting arterial structure. In infectious diseases, proteases play crucial roles in pathogen invasion and immune evasion. Neurodegenerative diseases are characterized by protease dysregulation, contributing to protein misfolding and aggregation. As research progresses, understanding the intricate relationships between proteases and diseases becomes essential for developing targeted therapeutic strategies. This review aims to provide a comprehensive glimpse into the diverse impact of protease activities on various diseases, emphasizing their potential as crucial players in the landscape of disease pathology and potential therapeutic interventions.

Phytosterols are bioactive substances found naturally in the cell membranes of plants and have an arrangement of molecules similar to that of fat, which is produced by mammalian cells. They are widely distributed as dietary sources of lipids in plants, such as nuts, seeds, olive oil, and legumes. This review provides a summary of the efficacy of BS in treating lifestyle problems, as well as an appraisal of previous research. Data was collected from PubMed, ScienceDirect, Scopus, and Google scholar (1968 -2024) using standard keywords "β-sitosterol," "Classification," "Biosynthesis," "Pharmacokinetics," "Herbal nutraceutical," "Analytical," "Structure," "Pharmacological effect." A total of 222 studies were included in this review. Numerous in vitro and in vivo investigations have shown that BSs exhibit several biological properties such as calming and anxiolytic effects; narcotic and immune-stimulating effects; antibacterial, antineoplastic, inflammation-causing, lipid-lowering, and hepatoprotective effects; and antioxidant, anti-diabetic, and wound-healing effects in contrast to respiratory and non-alcoholic fatty liver disease illnesses. β-sitosterol is a promising natural substance for the management of cholesterol and inflammation. However, further studies are needed to understand its pharmacological consequences and determine its best use in clinical applications. β-Sitosterol, also known as "plant sterol ester," is often present in plants and has several applications, notably in medicine and the food industry. Experimental research on β-sitosterol provides unequivocal evidence that phytosterol can be supplemented with other methods to combat serious illnesses. Such a high potential identifies this substance as a noteworthy medication for the future based on its composition. Although β-sitosterol has anticancer and anti-inflammatory properties and is useful in human clinical trials for enlarged prostates, its mechanism of action remains unclear.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Introduction: The macrolide-resistant Bordetella pertussis (MRBp) has appeared in Asia and has even been prevalent in China. Since the antibiotic sensitivity test is not carried out in the clinical setting, macrolide is still the first choice of antibiotic in MRBp infection. Further, the macrolide therapy for pertussis needs to be revised. Macrolide has always shown a positive effect on other macrolide-resistant bacterium infections in clinical applications. However, the mechanism of macrolide on MRBp remains unclear.

Objective: The objective of this study was to investigate the effect of virulence of MRBp under the sub-MIC erythromycin.

Methods: This study evaluated a representative isolate BP19147 (ptxP1/fhaB3-MRBp) under a series of sub-inhibitory concentrations of erythromycin. We measured the growth curve, biofilm formation, and autoaggregation assay under Stainer and Scholte (SS) broth. The relative gene expression was detected by RT-qPCR.

Results: The proteomics was detected by label-fee DIA. The growth ability and virulence factors of MR isolate BP19147 were inhibited by sub-MIC of erythromycin and had a concentration- dependent effect. From the proteomics results, the pertussis toxin, filamentous haemagglutinin, and pertactin did not show a statistical difference (p >0.05). Other virulence factors (including dermonecrotic toxin, Invasive Adenylate cyclase/haemolysin. etc) showed a statistical difference (p <0.05). In the KEGG enrichment, the BvgAS system, biofilm formation, and some adaptive systems were inhibited by erythromycin.

Conclusion: The sub-MIC of erythromycin may reduce the virulence of MRBp, which will provide a theoretical basis for the rational use of erythromycin for MRBp infection and help the development of new antibiotics.