Unlocking ß-cell restoration: The crucial role of PDX1 in diabetes therapy.

Diabetes has been a significant healthcare problem worldwide for a considerable period. The primary objective of diabetic treatment plans is to control the symptoms associated with the pathology. To effectively combat diabetes, it is crucial to comprehend the disease's etiology, essential factors, and the relevant processes involving ß-cells. The development of the pancreas, maturation, and maintenance of ß-cells, and their role in regular insulin function are all regulated by PDX1. Therefore, understanding the regulation of PDX1 and its interactions with signaling pathways involved in ß-cell differentiation and proliferation are crucial elements of alternative diabetes treatment strategies. The present review aims to explore the protective role of PDX1 in ß-cell proliferation through signaling pathways. The main keywords chosen for this review include "PDX1 for ß-cell mass," "ß-cell proliferation," "ß-cell restoration via PDX1," and "mechanism of PDX1 in ß-cells." A comprehensive literature search was conducted using various internet search engines, such as PubMed, Science Direct, and other publication databases. We summarize several approaches to generating ß-cells from alternative cell sources, employing PDX1 under various modified growth conditions and different transcriptional factors. Our analysis highlights the unique potential of PDX1 as a promising target in molecular and cell-based therapies for diabetes.

Natural products in the management of neurodegenerative diseases.

Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

Decoding and Unravelling Mpox, Herpes, and Syphilis Infections: A State of Art Review.

As the world recovers from the COVID-19 pandemic, a resurgence in MPXV cases is causing serious concern. The early clinical similarity of MPXV to common ailments like the flu and cold, coupled with the resemblances of its progressing rash to other infections, underscores the importance of prompt and accurate diagnosis. Among the infections, smallpox is clinically closest to MPXV, and rashes similar to MPXV stages also appear in syphilis and varicella zoster. A comprehensive review of MPXV, herpes, and syphilis was carried out, including structural and morphological features, origins, transmission modes, and computational studies. PubMed literature search on MPXV, using MeSH key terms, yielded 1904 results, with the analysis revealing prominent links to sexually transmitted diseases. More in-depth exploration of MPXV, Herpes Simplex Virus (HSV), and Syphilis revealed further disease interconnections and geographical correlations. These findings emphasize the need for a holistic understanding of these interconnected infectious agents for better control and management.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Natural Products-based Drugs: Potential Drug Targets Against Neurological Degeneration.

Phytochemicals or natural products have been studied extensively for their potential in the treatment of neurodegenerative diseases (NDs) like Parkinson's disease, Alzheimer's disease, etc. The neuronal structure loss and progressive dysfunction are the main characteristics of these diseases. In spite of impressive and thorough knowledge of neurodegenerative molecular pathways, little advancement has been found in the treatment of the same. Moreover, it was proved that natural products can be used efficiently in the treatment of NDs while certain issues regarding the patient's safety and clinical data are still existing. As ND is a bunch of diseases and it will start the myriad of pathological processes, active targeting of the molecular pathway behind ND will be the most efficient strategy to treat all ND-related diseases. The targeting pathway must prevent cell death and should restore the damaged neurons. In the treatment of ND and related diseases, natural products are playing the role of neuroprotective agents. This review will target the therapeutic potential of various phytochemicals which shows neuroprotective action.

Nanocarriers and Diabetes: New Vistas and the Way Ahead.

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.

Dietary Supplementation with Resveratrol Attenuates Serum Melatonin Level, Pro-Inflammatory Response and Metabolic Disorder in Rats Fed High-Fructose High-Lipid Diet under Round-the-Clock Lighting.

This study aims to investigate the effect of resveratrol on systemic inflammatory response and metabolic disorder in rats fed a high-fructose high-lipid diet (HFHLD) and exposed to round-the-clock lighting (RCL). 21 adult male Wistar rats were randomly divided into 3 groups: control (group 1, n = 7); HFHLD for 8 weeks + round-the-clock lighting (RCL) (group 2, n = 7); HFHLD + RCL + Resveratrol (in a daily dose of 5 mg/kg intragastrically (group 3, n = 7). Results show that the combined effect of HFHLD and RCL reduces the serum melatonin (p < 0.001) and accelerates pro-inflammatory activities, oxidative stress, and metabolic disorder. There is a significant increase in the serum tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) (both p < 0.001), blood malondialdehyde-thiobarbituric acid adducts (MDA-TBA2) (p < 0.001), serum glucose (p < 0.01), insulin concentration, and the homeostatic model assessment insulin resistance (HOMA-IR) index (both p < 0.001), serum with very low-density lipoprotein (VLDL), and triacylglycerol (TAG) (both p < 0.001). At the same time, the decrease in the serum high-density lipoprotein (HDL) level (p < 0.001) is observed in the HFHLD + RCL group compared to the control. In the HFHLD + RCL + Resveratrol group, hypomelatonaemia (p < 0.001), pro-inflammatory actions, oxidative stress, and metabolic disorder were mitigated. Resveratrol can cause a significant rise in the serum melatonin and reduce serum TNF-α and CRP levels (both p < 0.001), blood MDA-TBA2 (p < 0.001), serum glucose (both p < 0.01), insulin concentration, and HOMA-IR (both p < 0.001), serum VLDL and TAG (both p < 0.001) compared to the group 2, while serum HDL level increases (p < 0.01). Resveratrol attenuates pro-inflammatory responses and prevents considerable metabolic disorder in rats fed HFHLD under RCL.

Nanomedicine: Innovative Strategies and Recent Advances in Targeted Cancer Therapy.

Nanomedicine's application of nanotechnology in medicine holds tremendous potential for diagnosing and treating life-threatening diseases such as cancer. Unlike conventional therapies, nanomedicine offers a promising strategy to enhance clinical outcomes while minimizing severe side effects. The principle of drug targeting enables specific delivery of therapeutic agents to their intended sites, making it a more precise and effective therapy. Combination strategies, such as the co-delivery of chemotherapeutic drugs with nucleic acids or receptor-specific molecules, are being employed to enhance therapeutic outcomes. Nanocarriers and drug delivery systems designed using these approaches offer resourceful co-delivery of therapeutic agents for anticancer therapy. Targeted drug delivery via nanotechnology-based techniques has become an urgent need and has shown significant improvements in therapeutic implications, pharmacokinetics, specificity, reduced toxicity, and biocompatibility. This review discusses the extrapolation of nanomaterials for developing innovative and novel drug delivery systems for effective anticancer therapy. Additionally, we explore the role of nanotechnology-based concepts in drug delivery research.

Celiac disease: Pathogenesis, disease management and new insights into the herbal-based treatments.

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

Identification and evaluation of antimicrobial and anti-arthritis activities of hydroethanolic extract of Rubus ellipticus leaves.

Rubus ellipticus is a native plant to India's tropical and subtropical regions and has been used as a traditional medicinal. The aim of study was to identify and evaluate the antimicrobial and anti-arthritis activities of hydroethanolic extract of R. ellipticus leaves (HEERE). The leaves were collected from the Narkanda Valley, India and were shade-dried and finely ground to produce the powder. The hydroethanolic extract was utilized for phytochemical analysis to determine the existence of carbohydrate, phenolic, terpenoid, flavonoid, saponin, glycoside, tannin, protein, and alkaloid. The HEERE was futher analyzed by gas chromatography-mass spectrometry (GC-MS) for the characterization of the phytoconstituents. The antimicrobial activity was tested against Escherichia coli, Staphylococcus aureus as well as Aspergillus niger. To assess its anti-arthritic activities, different doses of HEERE were given orally to complete Freund's adjuvant (CFA)-induced albino Wistar rats for twenty-one days. The GC-MS analysis of hydroethanolic extracts from leaves detected and identified the presence of 33 phytochemical compounds. HEERE showed significant effects against E. coli, S. aureus, and A. niger strains at 600 ppm. Our data indicated that HEERE 200 mg/kg was more effective than 50 mg/kg as anti-arthritis. Paw volume, ankle-joint diameter, the number leucocytes, and erythrocyte sedimentation rate (ESR) were all significantly reduced in experimental rats. Furthermore, when compared to respective standard drugs, the body weight, erythrocyte, hemoglobin, and synobium healing effect have all improved. These data demonstrated the potential of R. ellipticus for the long-term investigation of antimicrobial and anti-arthritic properties.

Aducanumab in Alzheimer's disease: A critical update.

Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aß (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.

Research progress of small-molecule drugs in targeting telomerase in human cancer and aging.

Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.

Recent Advances of Nanotechnology in the Diagnosis and Therapy of Triple- Negative Breast Cancer (TNBC).

BACKGROUND: The development of advanced treatment of triple-negative breast cancer (TNBC) is the utmost need of an era. TNBC is recognized as the most aggressive, metastatic cancer and the leading cause of mortality in females worldwide. The lack of expression of triple receptors namely, estrogen, progesterone, and human epidermal receptor 2 defined TNBC. OBJECTIVE: The current review introduced the novel biomarkers such as miRNA and family, PD1, EGFR, VEGF, TILs, P53, AR and PI3K, etc. contributed significantly to the prognosis and diagnosis of TNBC. Once diagnosed, the advanced utilization approaches are available for TNBC because of the limitations of chemotherapy. Novel approaches include lipid-based (liposomes, SLN, NLC, and SNEDDS), polymer-based (micelle, nanoparticles, dendrimers, and quantum dots), advanced nanocarriers such as (exosomes, antibody and peptide-drug conjugates), and carbonbased nanocarriers (Carbon nanotubes, and graphene oxide). Lipid-based delivery is used for excellent carriers for hydrophobic drugs, biocompatibility, and lesser systemic toxicities than chemotherapeutic agents. Polymer-based approaches are preferred over lipids for providing longer circulation time, nanosize, high loading efficiency, high linking, avoiding the expulsion of drugs, targeted action, diagnostic and biosensing abilities. Advanced approaches like exosomes, conjugated moieties are preferred over polymeric for possessing potency, high penetrability, biomarkers, and avoiding the toxicity of tissues. Carbon-based gained wide applicability for their unique properties like a versatile carrier, prognostic, diagnostic, sensing, photodynamic, and photothermal characteristics. CONCLUSION: The survival rate can be increased by utilizing several kinds of biomarkers. The advanced approaches can also be significantly useful in the prognosis and theranostic of triplenegative breast cancer. One of the biggest successes in treating with nanotechnology-based approaches is the marked reduction of systemic toxicity with high therapeutic effectiveness compared with chemotherapy, surgery, etc. The requirements such as prompt diagnosis, longer circulation time, high efficiency, and high potency can be fulfilled with these nanocarriers.

Application of Artificial Intelligence in Drug Discovery.

Due to the heap of data sets available for drug discovery, modern drug discovery has taken the shape of big data. Usage of Artificial intelligence (AI) can help to modify drug discovery based on big data to precised, knowledgeable data. The pharmaceutical companies have already geared their departments for this and started a race to search for new novel drugs. The AI helps to predict the molecular structure of the compound and its in-vivo vs. in-vitro characteristics without hampering life, thus saving time and economic loss. Clinical studies, electronic records, and images act as a helping hand for the development. The data mining and curation techniques help explore the data with a single click. AI in big data analysis has paved the red carpet for future rational drug development and optimization. This review's objective is to familiarise readers with various advances in the AI field concerning software, firms, and other tools working in easing out the labor of the drug discovery journey.

Insights on prospects of nano-siRNA based approaches in treatment of Cancer.

siRNA interference, commonly referred to as gene silence, is a biological mechanism that inhibits gene expression in disorders such as cancer. It may enhance the precision, efficacy, and stability of medicines, especially genetic therapies to some extent. However, obstacles such as the delivery of oligonucleotide drugs to inaccessible areas of the body and the prevalence of severe side effects must be overcome. To maximize their potential, it is thus essential to optimize their distribution to target locations and limit their toxicity to healthy cells. The action of siRNA may be harnessed to delete a similar segment of mRNA that encodes a protein that causes sickness. The absence of an efficient delivery mechanism that shields siRNA from nuclease degradation, delivers it to cancer cells and releases it into the cytoplasm of specific cancer cells without causing side effects is currently the greatest obstacle to the practical implementation of siRNA therapy. This article focuses on combinations of siRNA with chemotherapeutic drug delivery systems for the treatment of cancer and gives an overview of several nanocarrier formulations in both research and clinical applications.

WITHDRAWN: Current Synopsis on siRNA Therapeutics as a Novel Anti-Cancer and Antiviral Strategy: Progress and Challenges

The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Biotechnology.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Metabolomics and EMT Markers of Breast Cancer: A Crosstalk and Future Perspective.

Cancer cells undergo transient EMT and MET phenomena or vice versa, along with the parallel interplay of various markers, often correlated as the determining factor in decoding metabolic profiling of breast cancers. Moreover, various cancer signaling pathways and metabolic changes occurring in breast cancer cells modulate the expression of such markers to varying extents. The existing research completed so far considers the expression of such markers as determinants regulating the invasiveness and survival of breast cancer cells. Therefore, this manuscript is crosstalk among the expression levels of such markers and their correlation in regulating the aggressiveness and invasiveness of breast cancer. We also attempted to cover the possible EMT-based metabolic targets to retard migration and invasion of breast cancer.

Neurobehavioral and Biochemical Evidences in Support of Protective Effect of Marrubiin (Furan Labdane Diterpene) from Marrubium vulgare Linn. and Its Extracts after Traumatic Brain Injury in Experimental Mice.

Traumatic brain injuries due to sudden accidents cause major physical and mental health problems and are one of the main reasons behind the mortality and disability of patients. Research on alternate natural sources could be a boon for the rehabilitation of poor TBI patients. The literature indicates the Marrubium vulgare Linn. and its secondary metabolite marrubiin (furan labdane diterpene) possess various pharmacological properties such as vasorelaxant, calcium channel blocker, antioxidant, and antiedematogenic activities. Hence, in the present research, both marrubiin and hydroalcoholic extracts of the plant were evaluated for their neuroprotective effect after TBI. The neurological severity score and oxidative stress parameters are significantly altered by the test samples. Moreover, the neurotransmitter analysis indicated a significant change in GABA and glutamate. The histopathological study also supported the observed results. The improved neuroprotective potential of the extract could be attributed to the presence of a large number of secondary metabolites including marrubiin.

Fungal Mushrooms: A Natural Compound With Therapeutic Applications.

Fungi are extremely diverse in terms of morphology, ecology, metabolism, and phylogeny. Approximately, 130 medicinal activities like antitumor, immunomodulation, antioxidant, radical scavenging, cardioprotective and antiviral actions are assumed to be produced by the various varieties of medicinal mushrooms. The polysaccharides, present in mushrooms like ß-glucans, micronutrients, antioxidants like glycoproteins, triterpenoids, flavonoids, and ergosterols can help establish natural resistance against infections and toxins.. Clinical trials have been performed on mushrooms like Agaricus blazei Murrill Kyowa for their anticancer effect, A. blazei Murrill for its antihypertensive and cardioprotective effects, and some other mushrooms had also been evaluated for their neurological effects. The human evaluation dose studies had been also performed and the toxicity dose was evaluated from the literature for number of mushrooms. All the mushrooms were found to be safe at a dose of 2000 mg/kg but some with mild side effects. The safety and therapeutic effectiveness of the fungal mushrooms had shifted the interest of biotechnologists toward fungal nanobiotechnology as the drug delivery system due to the vast advantages of nanotechnology systems. In complement to the vital nutritional significance of medicinal mushrooms, numerous species have been identified as sources of bioactive chemicals. Moreover, there are unanswered queries regarding its safety, efficacy, critical issues that affect the future mushroom medicine development, that could jeopardize its usage in the twenty-first century.

Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies.

Endometrial cancer (EC) is the sixth most prevalent type of cancer among women. Kinases, enzymes mediating the transfer of adenosine triphosphate (ATP) in several signaling pathways, play a significant role in carcinogenesis and cancer cells' survival and proliferation. Cyclin-dependent kinases (CDKs) are involved in EC pathogenesis; therefore, CDK inhibitors (CDKin) have a noteworthy therapeutic potential in this type of cancer, particularly in EC type 1. Natural compounds have been used for decades in the treatment of cancer serving as a source of anticancer bioactive molecules. Many phenolic and non-phenolic natural compounds covering flavonoids, stilbenoids, coumarins, biphenyl compounds, alkaloids, glycosides, terpenes, and terpenoids have shown moderate to high effectiveness against CDKin-mediated carcinogenic signaling pathways (PI3K, ERK1/2, Akt, ATM, mTOR, TP53). Pharmaceutical regimens based on two natural compounds, trabectedin and ixabepilone, have been investigated in humans showing short and midterm efficacy as second-line treatments in phase II clinical trials. The purpose of this review is twofold: the authors first provide an overview of the involvement of kinases and kinase inhibitors in the pathogenesis and treatment of EC and then discuss the existing evidence about natural products' derived kinase inhibitors in the management of the disease and outline relevant future research.