Current Pharmaceutical Biotechnology - Online First
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51 - 72 of 72 results
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COL1A1, COL1A2, CHN1, and FN1 Promote Tumorogenesis and Act as Markers of Diagnosis and Survival in Gastric Cancer Patients
Authors: Yan Yichao, Li Yongbai, Liang Hailiang, Chen Dongbo, Li Bo and Abduh MurshedAvailable online: 13 January 2025More LessObjectivesThis study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.
MethodologyGSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.
ResultsAnalysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis. Subsequent validation across The Cancer Genome Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls. Promoter methylation analysis revealed decreased methylation levels of these hubs in GC tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal showcased frequent mutations in these genes, particularly FN1, further highlighting their significance in GC pathogenesis. Survival analysis indicated their correlation with reduced overall survival rates among GC patients, supported by the development of a robust prognostic model. Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their regulatory mechanisms and downstream pathways, implicating their involvement in extracellular matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between hub gene expression and drug response, while RT-qPCR validation confirmed their up-regulation in clinical GC samples. Finally, functional assays demonstrated the impact of FN1 knockdown on cellular proliferation, colony formation, and wound healing capacities.
ConclusionOverall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic targets.
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Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer’s Disease
Authors: Chintan Aundhia, Ghanshyam Parmar, Chitrali Talele, Rahul Trivedi, Mamta Kumari and Jay ChudasamaAvailable online: 09 January 2025More LessAlzheimer’s disease (AD) remains a major challenge in developing effective treatments due to its complex pathophysiology, including the accumulation of amyloid-beta plaques and tau tangles. Small interfering RNA (siRNA) technology offers promise for targeted gene silencing, but effective delivery to the central nervous system remains a significant obstacle. Viral vectors have emerged as potent delivery vehicles for transporting siRNA to neural tissues. This review explores the utilization of viral vectors for siRNA delivery in AD, focusing on delivery strategies and challenges. We discuss the design and optimization of viral vectors, targeting strategies, and safety considerations. Additionally, we examine recent advancements and prospects for enhancing viral vector-mediated siRNA delivery in AD.
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Biomimetic Fe3O4 Nanozymes Promote Apoptosis in Breast Cancer Cell Lines via Free Radical Scavenging and Inhibition of RelA/p65
Authors: Deepa Mundekkad and William C. ChoAvailable online: 07 January 2025More LessIntroductionIron oxide nanozyme was synthesized from the fruit peel extract of pomegranate, which served as a reducing agent during the green synthesis. The scavenging of reactive oxygen species is often accompanied by immunomodulation following antiproliferative effects due to the crosstalk between the proteins involved in the inter-related signaling pathways.
MethodIn the current study, the green synthesized nanozyme was studied for its ability to induce apoptosis in breast cancer cell lines. The free radical scavenging effect of the nanozyme was reflected as an extension of its intrinsic endogenous enzyme-mimicking property.
Result & DiscussionThe cell cycle analysis revealed that the cell death induced by nanozyme mainly affected the G0/G1 phase. The expression of RelA/p65 and the inflammatory mediators affected by the nanozyme established the role of the Fe3O4 nanozyme in immunomodulation along with its antiproliferative activity.
ConclusionThis is the first report on the antiproliferative and immunomodulatory activities expressed by the biomimetic iron oxide nanozyme.
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The Exosome and its Application in Skin Wound Healing: A Systematic Review on In vitro Studies
Available online: 06 January 2025More LessBackgroundWound healing is a complex procedure frequently delayed in patients with underlying chronic conditions. Despite essential advances in tissue engineering and regenerative medicine, wound healing remains challenging, warranting novel methods for promoting wound healing. It has been demonstrated that exosomes are one of the main secretory products of different cell types, such as Mesenchymal Stem Cells (MSCs), for regulating various biological processes, including wound healing. Henceforth, understanding these exosome effects might assist in improving wound management and highlight a novel therapeutic model for cell-free therapies with reduced side effects for repairing wounds.
MethodsThis systematic review involved conducting research electronically on scholarly scientific databases, including PubMed, Science Direct, and Scopus. Eligibility checks were performed based on predefined selection criteria. Finally, thirty-nine studies were considered.
ResultsExosomes have been indicated to use multitargeted pathways to improve wound healing by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, metastasis, apoptosis, and angiogenesis.
ConclusionThe outcome of this review might guide pre-clinical and clinical studies on the role of exosomes in skin wound healing.
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In vitro Investigation of Antimicrobial and Antioxidant Properties of Green Silver Nanoparticles Synthesized Using Ephedra gerardiana Plant Extract
Available online: 06 January 2025More LessBackgroundThe increasing prevalence of antibiotic-resistant bacteria necessitates exploring nanotechnology as a potential solution for microbial elimination.
ObjectivesThis study aimed to investigate the antimicrobial and antioxidant effects of silver nanoparticles synthesized using aqueous extract from the Ephedra gerardiana (E. gerardiana) plant (EG@AgNPs).
MethodsOptimal synthesis conditions, including silver nitrate concentration, time, and temperature, were determined. Characterization of EG@AgNPs was conducted, which was followed by antimicrobial assessment against eight bacterial strains and one fungal strain. Additionally, the antioxidant properties of EG@AgNPs were evaluated using the DPPH method.
ResultsXRD analysis confirmed EG@AgNPs synthesis. DLS analysis revealed a hydrodynamic diameter of 22 nm. FT-IR analysis confirmed the presence of functional groups from the E. gerardiana plant extract in EG@AgNPs. FESEM and TEM images depicted spherical nanoparticles ranging in size from 10 to 20 nm. Antimicrobial investigations using the broth microdilution method demonstrated that E. gerardiana plant extract at 7.5 mg/ml inhibited only Streptococcus mutans and Candida albicans growth, with no antimicrobial effects observed at lower concentrations. However, EG@AgNPs significantly enhanced the antimicrobial properties of the E. gerardiana plant extract. Notably, these nanoparticles exhibited the most significant effect on E. coli and the least on S. salivaris, with MIC value of 125 and 2000 µg/ml, respectively. Furthermore, they inhibited C. albicans growth at a concentration of 62.5 μg/ml. An assessment of the antioxidant properties of EG@AgNPs indicated a significant increase in antioxidant activity.
ConclusionThe E. gerardiana plant extract has emerged as a promising option for silver nanoparticle synthesis. These nanoparticles have been found to exhibit potent antimicrobial properties against Gram-positive and Gram-negative bacterial species, as well as C. albicans. Additionally, they have demonstrated antioxidant properties.
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Strengthening Effect of Thalidomide Combined with an Anti-PD1 Antibody on Enhancing Immunity for Lung Cancer Therapy
Authors: Qing Liu, Zu-Chian Chiang, Xiangqian Zhao, Dongya Cui, Xinxin Li, Hao Chen, Fangyu Lin, Tao Jiang, Qi Chen, Xiaoyan Lin and Jizhen LinAvailable online: 03 January 2025More LessObjectiveCombining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis.
MethodsWe investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis.
ResultsTHD exhibited regulatory effects on PD-1 in CD4+ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4+ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4+ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8+ T cell infiltration in tumors, and reduced CD34+ intratumoral microvessel density.
ConclusionThis study highlights THD’s role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.
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CAR-T Cell Therapy: Pioneering Immunotherapy Paradigms in Cancer Treatment
Authors: Dhitri Borah, Sibasree Hojaisa, Indira Sarma, Anil Kumar Mavi, Tejveer Singh, Anita Gulati, Ravi, Kumar Goswami and Saurabh MaruAvailable online: 01 January 2025More LessThe world's one of the major causes of death are cancer. Cancer is still a complex disease over the years that needs to be cured. Traditional cytotoxic approaches, although they have been implemented for years for treating neoplastic diseases, yet are limited due to the intricacy and low efficiency of cancer cells. Researchers are thus compelled to seek more potent therapeutic strategies. Chimeric antigen receptor (CAR-T) cell therapy is one such innovative insight where T lymphocytes are altered genetically to target cancer cells. Despite the outstanding accomplishment in patients with haematological malignancies, CAR-T cell treatment has demonstrated minimal impact on solid tumours due to a number of obstacles, including proliferation, stability, trafficking, and fate within tumors. Furthermore, interactions between the host and tumour microenvironment with CAR-T cells significantly alter CAR-T cell activities. Designing and implementing these treatments additionally also requires a complex workforce. Overcoming these significant challenges, there is a requirement for innovative strategies for developing CAR-T cells with greater anti-tumour efficacy and reduced toxicity. In this chapter, the current advancement in CAR-T cell technology in order to increase clinical efficacy in both solid tumors and haematological, as well as possibilities to conquer the limits of CAR-T cell therapy in both solid and haematological tumours has been discussed.
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Effect of Ficus Carica and Zea Mays on Calcium Release from Oxalocalcic Urinary Calculi Using the Potentiometric Method
Available online: 30 December 2024More LessIntroductionA stone is a compact mass of one or more crystallised substances. The essential mechanism of stone formation is an excessive concentration of poorly soluble compounds in the urine. In excessive concentration, these compounds precipitate into crystals, which then aggregate to form a stone. The use of certain plants using the turbidimetric model has shown positive results on oxalocalcic crystallisation and, according to a recent study, has revealed very high inhibition rates.
AimThe aim of this study was to dissolve calcium oxalate urinary stones using two medicinal plants with high inhibition rates by monitoring Ca2+ release, pH variation, and mass loss. The study consisted of treating the stones with two plants, Ficus-carica and Zea mays, at two concentrations of 10g/l and 25g/l for 24 hours.
MethodThe main analytical techniques used in this study were as follows: Morphological analysis using a binocular magnifying glass, Fourier transform infrared spectroscopic method, and potentiometric method along with specific calcium electrode and an analytical balance. The study on the release of Ca2+ in the presence of the different herbal teas during 8 treatments of 3 to 4 hours was carried out on a series of 33 stones with the same chemical composition from several spontaneous expulsions of a 43-year-old male subject with lithiasis.
ResultsThe results showed a very remarkable effect of the Ficus-carica plant on Ca2+ release, which recorded 156.98 ppm, while Zea mays gave 130.63 ppm.
ConclusionThe kinetics of Ca2+ release were monitored by a potentiometer using a Ca2+-specific electrode. Zea mays at 10g/l showed a slightly positive effect on calculus dissolution compared to Ficus-carica.
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Advances and Challenges of Microneedle Assisted Drug Delivery for Biomedicals Applications: A Review
Authors: Shiv Bahadur, Radhika, Kantrol Kumar Sahu and Arun Kumar SinghAvailable online: 04 November 2024More LessMicroneedles have been explored as a novel way of delivering active ingredients into the skin. They have various advantages, such as quick and efficient drug delivery, mechanical stability, minimal pain, variable capacity and easy use. Microneedles are enabled for the delivery of vaccine, peptides, medicinal components and in cosmetology, which couldn’t go unnoticed. The novel approaches in the transdermal drug delivery system have increased the efficiency of drug delivery into the skin by crossing the skin barriers. This platform has a wide range of applications and can also be used to deliver non-transdermal biomedicals. The variety in the design of microneedles has demanded similar diversity in their methods of fabrication; micro molding and drawing lithography may be useful methods. There are different types of polymers and materials for the fabrication of microneedles. Several synthetic and natural materials are used in the fabrication of microneedles. Unique shapes, materials, and mechanical properties are modified for organ-specific applications in microneedle engineering. In this review, we discuss several factors and their roles to cross the biological barriers for transdermal drug delivery in various sites, such as in ocular, vascular, oral, and mucosal tissue. Additionally, this article highlights the future scope of transdermal drug delivery systems through microneedles.
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Influence of Nanomedicine as a Smart Weapon on Multidrug Resistance in Cancer Therapy
Authors: Safal Kumar Paikray, Liza Sahoo, Nigam Sekhar Tripathy and Fahima DilnawazAvailable online: 31 October 2024More LessCancer is the leading cause of death worldwide. The effectiveness of chemotherapy in cancer patients is still significantly hampered by Multidrug Resistance (MDR). Tumors exploit the MDR pathways to invade the host and limit the efficacy of chemotherapeutic drugs that are delivered as single drugs or combinations. Further, overexpression of ATP-binding Cassette transporter (ABC transporter) proteins augments the efflux of chemotherapeutic drugs and lowers their intracellular accumulation. Recent progress in the development of nanotechnology and nanocarrier-based drug delivery systems has shown a better perspective with respect to the improvement of cancer chemotherapy. Nanoparticles/nanomaterials are designed to target the immune system and tumor microenvironment of cancer cells for a variety of cancer treatments in order to improve bioavailability and reduce toxicity. This review elucidates the successful use of nanomaterials for cancer therapy and addressing the MDR and throws some light on the present obstacles impeding their translation to clinical use.
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Considerations and Challenges to Develop Drug-drug Coamorphous System: A Recent Update
Authors: Madhura Tiwari, Kavita Singh and Bappaditya ChatterjeeAvailable online: 30 October 2024More LessPoor water solubility of several drugs, especially BCS class II and IV drugs, restricts their dissolution and negatively affects oral absorption. Amorphization of drugs is a year-old approach to enhance solubility and dissolution of poorly water-soluble drugs. Polymeric amorphous systems have been proven effective but have disadvantages, such as low drug loading, high carrier content, etc. In a coamorphous system, a small molecule can be used as a coformer that keeps the amorphous form of a drug stable. In a drug-drug coamorphous system (CAS), one therapeutically active moiety can act as a coformer for the other drug. Although effective, the rationale of selecting the drugs and optimising the ratio without compromising therapeutic effect and safety is challenging. The preparation method is also a challenge because the stress during the processing method may result in the loss of crystallinity. Hence, the processing stability of the amorphous drug is a significant concern. A stable CAS is formed when two drugs generate some molecular-level interaction. In silico prediction of miscibility, molecular dynamic simulation, functional group analysis by Fourier Transform infrared spectroscopy, Raman spectroscopy, NMR, etc. contribute to the analysis of molecular-level interaction. Additionally, the article discusses the preparation method and the fact that the excipient must be selected carefully to form an effective CAS.
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Virus-like Particles-Based Vaccine to Combat Neurodegenerative Diseases
Available online: 29 October 2024More LessNeurodegenerative diseases are regarded as gradual, incurable conditions with an insidious onset. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two of the most prevalent neurodegenerative diseases reported globally. Developing effective treatment strategies for neurodegenerative diseases has remained a primary objective and a huge challenge for researchers. The therapeutic medications that are now approved for the treatment of neurodegenerative diseases merely treat the symptoms; the underlying pathology is not addressed. Therefore, the emergence of novel disease-modifying therapeutic modalities such as immunotherapy has opened a new path in developing effective treatments for neurogenerative diseases. Compared to other types of subunit active vaccines, virus-like particles (VLPs) are considerably more immunogenic as they present dense and repetitive viral antigen epitopes on their surface, which can trigger both humoral and cell-mediated immune responses. They are also a much safer option than the traditional inactivated and live-attenuated vaccines since they are devoid of viral genomes and are, therefore, non-pathogenic and non-infectious. Researchers have turned their attention to VLPs as an active immunotherapy candidate for AD due to the lessons learned from the AN1792 trial. Studies have shown that they effectively induce anti-Aβ, anti-tau, and anti-α-Synuclein antibodies while avoiding T-cell-related immune reactions in animal models of AD and PD. This review compiles the findings of preclinical animal model studies and clinical investigations on VLP-based vaccines for neurogenerative diseases thus far. The technical limitations and potential difficulties associated with the future application of VLP-based vaccines in patients with neurodegenerative diseases have also been covered.
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Tryptophan Stability and Palatability in the Food Formulation: A Review
Available online: 29 October 2024More LessTryptophan, an essential amino acid, plays a vital role in the synthesis of critical compounds like serotonin, melatonin, and niacin, which impact mood, sleep, and metabolic processes. It holds promise for improving the well-being of individuals with mood issues or sleep disorders through dietary enrichment. However, incorporating tryptophan into food products presents challenges related to stability, bitterness, and susceptibility to oxidative degradation. These issues can reduce consumer acceptability and effectiveness and may lead to the formation of harmful byproducts. This review comprehensively examines innovative strategies for enriching food products with tryptophan. Crucial approaches include using nano-emulsion systems to encapsulate tryptophan, thereby protecting it from environmental factors and enhancing its bioavailability, adding antioxidants to prevent degradation, and utilizing functional derivatives as alternatives to pure tryptophan. These strategies aim to improve the stability of tryptophan, reduce bitterness, and enhance consumer acceptability. This review provides valuable insights into practical methods for incorporating tryptophan into food formulations, with the goal of optimizing its health benefits and ensuring a positive consumer experience.
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SIRT3, a New Hope in Liver Diseases from Pathogenic Mechanisms to Therapeutic Strategies
Authors: Sai-Ya Tan, Xiao-Xuan Chen, Rui Zhang, Pan Liu, Jian-Peng Wang, Ting Wang, and and Zhang-E XiongAvailable online: 24 October 2024More LessThe 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.
ObjectivesThis 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.
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Revolutionizing Influenza Treatment: A Deep Dive into Targeted Drug Delivery Systems
Authors: Sourav Ghosh, Sejuti Ray Chowdhury, Monosiz Rahaman, Biswajit Basu and Bhupendra PrajapatiAvailable online: 21 October 2024More LessInfluenza, 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.
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Discovery of New Natural Phytocompounds: The Modern Tools to Fight Against Traditional Bacterial Pathogens
Available online: 21 October 2024More LessOngoing 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.
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Bridging the GAP: Probiotic Douches Redefining the Feminine Hygiene
Authors: Akash Kumar, Sadique Hussain, Nitya Srivastava, Gurvinder Singh, Monica Gulati and Rajesh KumarAvailable online: 09 October 2024More LessVaginal 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.
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Integrated Transcriptomics and Metabolomics Studies Reveal Steroid Biosynthesis Pathway and BCL2 Inhibitory Diazo-Progesterone of Drimia indica for Conservation and Sustainable Utilization
Authors: Vivek Shit, Mahesh Kumar Dhakar and Manoj KumarAvailable online: 09 October 2024More LessBackgroundThis 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.
MethodsThe 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.
ResultsThe 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.
ConclusionThis 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.
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Jiangu Recipe Suppresses ER Stress-Induced Apoptosis and Inhibits Extracellular Matrix Degradation in Chondrocytes through Upregulating SIRT1 Expression
Authors: Jie Qiao, Chang Cheng, Gongxu Yang, Chuanqi Zhong, Jun Jin and Bin WuAvailable online: 07 October 2024More LessObjectiveThis study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation.
MethodsChondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis-related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated.
ResultsJGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses.
ConclusionOur findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.
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Advances in Colon-Targeted Drug Delivery Systems: Innovative Strategies for Treating Colonic Disorders and Prospects for the Future
Authors: Jyoti Singh, Ashutosh Solanki, Gaurav Singh Sikarwar and Niraj Kumar SinghAvailable online: 07 October 2024More LessColon-specific targeting delivery systems have drawn a great deal of attention because they represent potential vehicles for treating colonic disorders like diverticulitis, colitis, salmonellosis, Crohn’s disease, etc. with less systemic adverse effects as well as for the better oral delivery of many therapeutics that are prone to enzymatic and acidic deterioration in the upper GI tract. Smart polymeric delivery systems in particular have been investigated as "intelligent" delivery systems capable of releasing entrapped pharmaceuticals at the proper time & site of action in response to certain physiological stimuli. The creation of novel polymers & crosslinkers with improved biodegradability and biocompatibility would expand and enhance applications now in use. The development of polymeric systems could result in more precise and programmable drug delivery/therapies. In addition, newer advancements have led to the development of numerous ground-breaking techniques for directing a medication molecule to the colon. This review highlighted formulation techniques pH-dependent, time-dependent, enzyme sensitive, magnetically dependent, ligand-receptor mediated, and microflora-activated systems. Moreover, several methods have been put forth that make use of the innovative idea of such delivery systems, and mechanisms in which the release of drugs is regulated by pH and time as well as pH and the colon's bacteria.
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The Gut Health Revolution: Herbs and Dietary Phytochemicals in Balancing Gut Microbiota for Optimal Human Health
Available online: 27 September 2024More LessThe gut microbiota is a varied population of microorganisms that live in the human gastrointestinal system. Emerging research emphasizes the importance of this microbial ecology in general health and its influence on a variety of disorders. The review explores the synergy between herbal treatment and traditional medicine, emphasizing their cultural significance and therapeutic benefits. It delves into the intricate relationship between herbal remedies, traditional healing practices, and their sustained usage over centuries. The review highlights the pivotal role of the gut microbiota in herbal medicine, elucidating how treatments influence the gastrointestinal microorganisms, impacting overall health. Dietary phytochemicals are underscored for their significance in herbal medicine and nutritional well-being, along with the interdependence of plant extracts and botanicals. The investigation explores the molecular connections between phytoconstituents and gut microbiota, aiming to deepen the understanding of herbal medicine's tailored approach to specific health challenges. The summary concludes by emphasizing herbal treatments' unique ability to regulate gut flora, contributing to overall gastrointestinal well-being. In closing, the review provides a concise overview, serving as a valuable resource for integrative medicine research, with recommendations for future exploration of herbal medicine's potential in healthcare.
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Biomarkers and Novel Therapies of Diabetic Neuropathy: An Updated Review
Available online: 27 September 2024More LessDiabetic neuropathy is a persistent consequence of the biochemical condition known as diabetes mellitus. As of now, the identification and management of diabetic neuropathy continue to be problematic due to problems related to the safety and efficacy of existing therapies. This study examines biomarkers, molecular and cellular events associated with the advancement of diabetic neuropathy, as well as the existing pharmacological and non-pharmacological treatments employed. Furthermore, a holistic and mechanism-centric drug repurposing approach, antioxidant therapy, Gene and Cell therapies, Capsaicin and other spinal cord stimulators and lifestyle interventions are pursued for the identification, treatment and management of diabetic neuropathy. An extensive literature survey was done on databases like PubMed, Elsevier, Science Direct and Springer using the keywords “Diabetic Neuropathy”, “Biomarkers”, “Cellular and Molecular Mechanisms”, and “Novel Therapeutic Targets”.Thus, we may conclude that non-pharmacological therapies along with palliative treatment, may prove to be crucial in halting the onset of neuropathic symptoms and in lessening those symptoms once they have occurred.
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