Current pharmaceutical biotechnology最新文献

Metabolic Syndrome (MetS) refers to the co-occurrence of a constellation of metabolic diseases in the same individual, such as abdominal/visceral obesity, insulin resistance or diabetes, alterations in the lipid profile (dyslipidemias), and/or hypertension, which promotes the development of other cardiometabolic and hepatic diseases. Dyslipidemia and metabolic dysfunction- associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), are common MetS pathologies closely related to lipid metabolism. Alterations in the metabolism of proteins, carbohydrates, and lipids, caused by an excessive intake of nutrients and abnormal accumulation of body fat, which promotes chronic low-grade inflammation, are pivotal aspects of MetS development. To avoid damage caused by lipid overaccumulation, the transcription factors responsible for regulating lipid homeostasis and inflammation (named in this work master regulators) must modify their regular activity; however, the high adiposity established for long periods causes the appearance of insulin resistance (the MetS triggering factor most widely accepted in the literature). Fortunately, scientific evidence suggests that the abnormal activity of these regulators can be conveniently modulated by distinct species of bioactive lipids, among which unsaturated fatty acids stand out, offering new alternatives for treating MetS. Therefore, this work aims to provide a general overview of scientific evidence that supports the mechanisms of action and the effective modulation by bioactive lipids of some master lipid-metabolism-and-inflammation regulators in diverse aspects of MetS.

The liver, the largest internal organ in the human body, regulates multiple reactions and processes, including detoxification, regeneration, and immune defense. Liver diseases have emerged as a significant global public health issue. Numerous studies have indicated that the mitochondrial deacetylase SIRT3 has played various roles in the pathogenesis and pathological progression of liver diseases. Objectives: This review aims to explore the advances in the study of SIRT3 and liver disease and review possible mechanisms. Natural and chemical activators of SIRT3 are also discussed. The role of SIRT3 in the pathogenic mechanisms and therapeutic strategies of liver disease is summarized by reviewing Pubmed. SIRT3 alleviates liver diseases by regulating fatty acid metabolism, mitochondrial function, and immune-inflammatory response. Meanwhile, Withaferin A, lipoic acid, major royal jelly proteins, and berberine can activate SIRT3 or upregulate its expression, thereby alleviating liver damage. SIRT3 can effectively slow down the progression of liver disease and protect the liver from further damage. The use of SIRT3 as a pharmacological target for the treatment of liver disease is a potential therapeutic approach.

Influenza, a highly transmissible respiratory infection caused by influenza viruses A and B, poses a persistent threat to global public health due to its high mutation rate, ability to develop resistance to existing antiviral drugs, and capacity for rapid spread. Current treatment options, including four main classes of antiviral agents-adamantanes, neuraminidase inhibitors, RNA-dependent RNA polymerase inhibitors, and polymerase acidic endonuclease inhibitors- are limited by the emergence of drug-resistant viral strains, non-specific drug distribution, and adverse side effects. Moreover, the effectiveness of traditional vaccines is often compromised by antigenic drift and shift, necessitating the development of alternative therapeutic strategies. This review comprehensively explores the potential of novel targeted drug delivery systems to address these limitations and improve influenza management. Nanotechnology-based platforms, including lipid-based, polymer-based, inorganic, and hybrid nanoparticles, offer enhanced drug delivery through improved bioavailability, targeted action, and controlled release, thus minimizing systemic toxicity and optimizing therapeutic outcomes. Inhalation delivery systems such as dry powder inhalers (DPIs), nebulizers, and nanotechnology-based inhalation formulations provide direct delivery of antiviral agents to the respiratory tract, ensuring rapid onset of action with reduced systemic side effects. Transdermal delivery methods, including microneedle patches and hydrogel-based systems, offer non-invasive alternatives that enhance patient compliance and allow for sustained drug release. Furthermore, this review discusses recent innovations, such as responsive drug delivery systems and multifunctional nanoparticles capable of simultaneous delivery of multiple therapeutic agents, representing a significant advancement in the fight against influenza. These novel approaches promise improved targeting and efficacy and enable personalized treatment strategies, enhancing patient outcomes in both seasonal flu and pandemic scenarios. Integrating these advanced drug delivery systems into clinical practice could revolutionize the management of influenza, offering a promising pathway toward more effective and safer therapies.

Ongoing competition between disease-causing bacteria and human hosts has resulted in the discovery of a wide array of antibacterials. The advent of antibacterials ushered in a promising period in the realm of microbiology, but its brilliance was short-lived and soon diminished. The excessive and incorrect use of antibacterials results in limited selection pressure on the targeted microorganisms, which in turn promotes the evolution of microbes instead of killing them. Consequently, antibacterial resistance has developed and given rise to strains that are resistant to many drugs, leading to a significant increase in mortality rates. The current review delves into the potential of novel natural phytocompounds as innovative solutions to combat these potential bacterial threats. The review begins by showcasing the modus operandi of conventional antibacterial drugs followed by addressing the mechanisms of resistance to antibacterial agents, which have significantly lowered the efficacy of conventional treatments. In contrast, the review explores the mechanism of antibacterial activity of plant-derived phytochemicals, unraveling the various ways in which natural compounds interact with bacterial targets. Furthermore, the review examines the synergism between plant phytochemicals and conventional antibiotics, showcasing the efficacy of this combinatorial approach in overcoming resistance. The review concludes by summarizing the current research and offering valuable insights into challenges in the use of plant phytochemicals as antibacterial therapeutics. This comprehensive overview reinforces the promise of incorporating modern scientific tools with traditional phytotherapy to develop effective strategies against resistant bacterial pathogens.

Background: Chemotherapy-induced alopecia (CIA) significantly impacts patients' emotional and psychological well-being and treatment regimen. Phenylephrine, a topical vasoconstrictor, can potentially reduce hair loss by limiting chemotherapy drug delivery to hair follicles. However, effective delivery of Phenylephrine through the skin remains challenging. This study investigates lipid vesicles as delivery vehicles to enhance Phenylephrine's skin permeation and sustained release due to their biocompatibility and encapsulation capabilities.

Objective: This study aimed to formulate and compare different lipid vesicles of Phenylephrine HCl for enhanced permeation through the skin for deep dermal delivery with sustained release of the drug so as to achieve local vasoconstriction.

Methods: Phenylephrine-loaded ethosomes, invasomes, and transfersomes were prepared and characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE %). These lipid vesicles were incorporated into hydrogels to facilitate sustained drug release to deep dermal layers where they could target local vasculature and cause vasoconstriction. The prepared vesicular gels were evaluated for various permeation parameters.

Results: The entrapment efficiencies of the developed vesicles ranged from 49.51 ± 3.25% to 69.09 ± 2.32%, with vesicle sizes ranging from 162.5 ± 5.21 nm to 321.32 ± 3.75 nm. Statistical analysis revealed significantly higher flux values (Jss, μg/cm2 h) of 0.6251, 0.6314, and 0.4075 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, compared to plain gel (0.1254) (p < 0.005). The enhancement factors were 4.9848, 5.0350, and 3.2496 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, indicating superior permeation abilities of ethosomal and invasomal formulations.

Conclusion: The results demonstrate that ethosomal and invasomal formulations were efficient in delivering the drug to deep dermal layers of skin in a sustained manner. These findings suggest that these Lipidic vesicles would be able to target the local vasoconstrictor to vasculature, causing reduced hair loss by limiting chemotherapy drug delivery to hair follicles and managing chemotherapy-induced alopecia.

Introduction: Liposomes were extensively used for cosmetics and pharmaceuticals due to their versatility, biocompatibility, and biodegradability, as well as the ability to encapsulate water-soluble and fat-soluble substances. However, some challenges remain unsolved, including poor stability, complex preparation process, limited encapsulation efficiencies (EE%) and drug loading capacity (DLC%).

Method: We herein prepared universal liquid proliposomes by rotary evaporation method and optimized formulations with different pH, glycerol content, ethanol content and preparation process.

Result: The EE% of water-soluble substances was above 85%, and the maximum DLC% was 37.5%. In 7 different conditions, the optimal formulation of the proliposomes remained stable over 60 days. The excellent stability of proliposomes and nicotinamide liposomes and their essence, when applied to cosmetic formulations, was confirmed by the Turbiscan stability analyzer.

Conclusion: The proposed universal liquid proliposomes can form liposomes encapsulating a variety of water-soluble substances rapidly, making them an accessible and versatile tool for improving the stability and applicability of water-soluble raw materials.

There is a rapid spread of Multiple Sclerosis disorder across the globe, around 2.8 million cases of Multiple Sclerosis in the world. Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by demyelination, neuroinflammation, and a wide spectrum of clinical manifestations. Many drugs have been tested on MS patients but there is no effective treatment for MS till now. So to inhibit the symptoms caused by MS we performed a study in which we identified various naturally occurring materials with neuroprotective effects on the body that can treat Multiple Sclerosis. The therapeutic strategies portion of the paper reviews the array of disease-modifying therapies currently available for MS management. This paper evaluated their mechanisms of action, efficacy, and safety profiles. It also addressed emerging treatment paradigms by using different naturally occurring materials, including personalized medicine approaches and novel therapies in development. This paper provides a comprehensive overview of the current state of knowledge regarding MS, focusing on its pathogenesis, diagnostic approaches, and therapeutic strategies.

Background: This study is the first report on the sequence of the transcriptome of Drimia indica, a non-model plant with medicinal properties found in a forest tribal belt, using the Illumina NovaSeq platform. The primary objectives of this study were to elucidate the gene expression profiles in different tissues, identify key regulatory genes and pathways involved in secondary metabolite biosynthesis, and explore the plant's potential pharmacological properties.

Methods: The study generated 670087 unigenes from both leaves and roots and identified putative homologs of annotated sequences against UniProt/Swiss-Prot and KEGG databases. The functional annotation of the identified unigenes revealed the secondary metabolite biosynthetic process as the most prominent pathway, with gene enrichment analysis predominantly accounting for secondary metabolite pathways, such as terpenoid, steroid, flavonoid, alkaloid, selenocompound, and cortisol synthesis. The study also identified regulatory genes NAC, Bhlh, WRKY, and C2H2 on the transcriptome dataset.

Results: The functionally annotated unigenes suggested phytocompounds in Drimia indica to have multi-potent properties, such as anti-cancer, anti-inflammatory, and anti-diabetic activities, which has been further validated by GC-MS-based metabolite profiling. Notably, we have identified two novel molecules, di-azo progesterone and 4H-pyran-4-one 2,3-dihydro-3,5-dihydroxy- 6-methyl, with potential BCL2 inhibitory anticancer properties, supported by stable binding interactions observed in molecular docking and dynamics simulations. Additionally, an abundance of mono-nucleotide SSR markers has been identified, useful for genetic diversity studies.

Conclusion: This study provides a foundational understanding of the molecular mechanisms in Drimia indica, highlighting its potential as a source for novel therapeutic agents and contributing valuable insights for future pharmacological and agricultural applications. However, further in vivo studies are warranted to confirm these findings and validate their pharmacological efficacy and therapeutic potential. The SSR markers identified also offer valuable tools for molecular genetics, plant breeding, and sustainable drug development.

Vaginal douching is a centuries-old practice which is still in use, especially among adolescents. "Probiotic douches" are the vaginal douches that are formulated with probiotics and are intended to restore or maintain the vaginal microbiome balance. Probiotic douches are a new type of feminine hygiene product that claims to promote a balanced vaginal microbiome and improve overall well-being. However, the evidence supporting the use of probiotics for vaginal health is limited because of the variability in probiotic strains and dosages studied, and the lack of more comprehensive, long-term clinical trials. Most of the existing scientific literature on probiotics focuses on oral probiotic supplements and vaginal probiotic suppositories. Some potential benefits of probiotic douches include restoring a balanced vaginal microbiota, preventing, or managing infections, supporting local immune function, reducing odor and discharge, and enhancing overall vaginal comfort. However, it is important to note that these benefits have not been definitively proven and remain a subject of ongoing research. There are also potential risks associated with their use including disruption of the natural vaginal ecosystem by introducing foreign substances, risk of infection, and stability issues with the formulation that may lead to negative consequences. This review attempts to comprehend the critical need for robust scientific research to guide the safe and effective incorporation of probiotic douches into modern feminine hygiene practices, revolutionizing women's health, and well-being.

Background: Inflammation serves as a protective response to combat cellular and tissue damage. There is currently a wide array of synthetic and traditional therapies available for the treatment of inflammatory diseases. However, it is necessary to create a drug delivery system based on nanotechnology that can improve the solubility, permeability, and bioavailability of current treatments. Mesoporous silica nanoparticles (MSNPs) are inorganic materials known for their organised porous interiors, high pore volumes, substantial surface area, exceptional selectivity, permeability, low refractive index, and customisable pore sizes.

Objective: This review offers concise insights into the progression of the pathophysiology of inflammation, as well as the inducers, mediators, and effectors that are involved in the inflammatory pathway. This study focuses on the growing significance of MSNPs in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing applications. This review also presents the latest information on the crucial role of MSNPs in delivering herbal medicines for the treatment of inflammation.

Methods: A comprehensive literature search was conducted for this aim, utilising the Google Scholar, PubMed, and ScienceDirect databases. A systematic review was undertaken utilising scholarly articles published in peer-reviewed journals from 2000 to 2024.

Results: The inflammatory mediators involved in the pathophysiology of inflammation include platelet-activating factor, lipoxygenase, cyclooxygenase, Interferon-α, interleukin-6, interleukin- 1β, matrix metalloproteinases, inducible nitric oxide synthase, nuclear factor-κB, prostaglandins, nitric oxide, and phospholipase A2. MSNPs have the potential to be used in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing. The investigation of the MSNPs of plant-based compounds such as berberine, tetrahydrocannabinol, curcumin, and resveratrol has shown successful results in recent years for the purpose of managing inflammation.

Conclusion: This review demonstrates that MSNPs have a strong potential to play a positive role in delivering synthetic and plant-based therapies for the treatment of inflammatory illnesses.