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Oral cancer is a disease with high mortality and rising incidence worldwide. Although fragmentary literature on the anti‐oral cancer effects of plant products has been published, a comprehensive analysis is lacking. In this work, a critical and comprehensive evaluation of oral cancer preventative or therapeutic effects of dietary plants was conducted. An exhaustive analysis of available data supports that numerous dietary plants exert anticancer effects, including suppression of cell proliferation, viability, autophagy, angiogenesis, invasion, and metastasis while promoting cell cycle arrest and apoptosis. Plant extracts and products target several cellular mechanisms, such as the reversal of epithelial‐to‐mesenchymal transition and the promotion of oxidative stress and mitochondrial membrane dysfunction by modulation of various signaling pathways. These agents were also found to regulate cellular growth signaling pathways by action on extracellular signal‐regulated kinase and mitogen‐activated protein kinase, inflammation via modulation of cyclooxygenase (COX)‐1, COX‐2, and nuclear factor‐κB p65, and metastasis through influence of cadherins and matrix metalloproteinases. In vivo studies support these findings and demonstrate a decrease in tumor burden, incidence, and hyperplastic and dysplastic changes. Clinical studies also showed decreased oral cancer risk. However, high‐quality studies should be conducted to establish the clinical efficacy of these plants. Overall, our study supports the use of dietary plants, especially garlic, green tea, longan, peppermint, purple carrot, saffron, tomato, and turmeric, for oral cancer prevention and intervention. However, further research is required before clinical application of this strategy. [ABSTRACT FROM AUTHOR]

Background: Valproic acid (VPA) is a widely used antiepileptic drug (AED) often prescribed as a first-line treatment for many idiopathic and symptomatic generalized epilepsies. Several studies have highlighted the side effects of VPA on male fertility and reproductive factors in males, although the specific underlying etiology of these abnormalities is not clear. The present systematic review and meta-analysis aimed to assess the preclinical and clinical evidence concerning the impact of VPA on male fertility and reproductive factors. Methods: The scientific literature was reviewed for eligibility using PubMed, Web of Science, and PsycINFO, encompassing preclinical and clinical studies. Factors related to male fertility and reproduction, such as differences in sperm count, sperm motility, and the percentage of abnormal sperm, were compared between the experimental groups treated with VPA (in both preclinical and clinical) and the control groups using the Standardized Mean Difference (SMD) with 95% confidence intervals (CIs). Additionally, differences in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were explicitly assessed in clinical studies. Results: Male fertility data were extracted from 7 preclinical studies (112 animals) and 5 clinical studies (274 male individuals). The results of animal studies found that the sperm count (SMD = -2.28, 95% CI: -3.39 to -1.18, P = 0.335) and sperm motility (SMD = -2.32, 95% CI: -3.34 to -1.30, P = 0.368) were decreased in the treated groups compared to the control groups. The percentage of abnormal sperm (SMD = 3.27, 95% CI: 1.98 to 4.56, P = 0.019) was significantly increased, while a non-significant reduction was revealed in the weight of the testis (SMD = -2.73, 95% CI: -4.23 to -1.23, P = 0.673) in treated groups. The outcomes of clinical studies indicated a non-significant decrease in sperm count (SMD = -0.78, 95% CI: -1.58 to 0.03, P = 0.286) among patients with epilepsy treated with VPA compared to control subjects. However, a significant reduction in sperm motility (SMD = -1.62, 95% CI: -2.81 to -0.43, P = 0.033 was observed. The percentage of abnormal sperm showed a non-significant increase (SMD = 0.93, 95% CI: -0.97 to 2.84, P = 0.616) after being treated with VPA. Furthermore, there was a non-significant reduction in the levels of FSH (SMD = -1.32, 95% CI: -2.93 to 0.29, P = 0.198) and LH (SMD = -0.96, 95% CI: -1.95 to 0.04, P = 0.211) observed in clinical participants. Conclusion: This meta-analysis of both preclinical and clinical studies revealed that VPA causes a significant reduction in male fertility and reproductive factors among male patients with epilepsy. Clinical neurologists should be more cautious when prescribing VPA, especially to young male adult patients with epilepsy. [ABSTRACT FROM AUTHOR]

Amid the growing challenge of antibiotic resistance on a global scale, there has been a notable resurgence in bacteriophage-based treatments, signaling a shift in our approach to managing infections. Bacteriophages (BPs), bacterial predators of nature, present a promising alternative for tackling infections caused by antibiotic-resistant pathogens. This review delves into the intricate relationship between bacteriophages and resistant bacteria, exploring various treatment strategies. Drawing upon both preclinical and clinical studies, the review highlights the effectiveness of bacteriophage therapy, particularly when integrated synergistically with conventional antibiotics. It discusses various treatment approaches for systemic and localized infections, demonstrating the adaptability of bacteriophage therapy across different clinical scenarios. Furthermore, the formulation and delivery of bacteriophages shed light on the various methods used to encapsulate and administer them effectively. It also acknowledges the challenge of bacterial resistance to bacteriophages and the ongoing efforts to overcome this hurdle. In addition, this review highlights the importance of the bacteriophage sensitivity profile (phagogram), which helps tailor treatment regimens to individual patients and specific pathogens. By surpassing the limitations of traditional antibiotics, bacteriophage-based therapies offer a personalized and potent solution against antibiotic resistance, promising to reshape the future of infectious disease management. [ABSTRACT FROM AUTHOR]

Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and undercarboxylated OC (ucOC). While cOC promotes bone mineralization and increases bone strength, ucOC is regarded an endocrinologically active form that may have several functions in multiple end organs and tissues. Total OC (tOC) includes both of these forms (cOC and ucOC) and is considered a marker of bone turnover in clinical settings. Most of the data on OC is limited to preclinical studies and therefore may not accurately reflect the situation in clinical conditions. For the stated reason, the aim of this review was not only to summarize current knowledge of all forms of OC and characterize its role in diabetes mellitus, osteoporosis, osteopetrosis, inflammatory joint diseases, but also to provide new interpretations of its involvement in the management and treatment of aforementioned diseases. In this context, special emphasis was placed on available clinical trials. Significantly lower levels of tOC and ucOC could be associated with the risk of type 2 diabetes mellitus. On the contrary, tOC level does not seem to be a good indicator of high bone turnover status in postmenopausal osteoporosis, osteoarthritis and rheumatoid arthritis. The associations between several pharmacological drugs used to treat all disorders mentioned above and OC levels have also been provided. From this perspective, OC may serve as a medium through which certain medications can influence glucose metabolism, body weight, adiponectin secretion, and synovial inflammation. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models. [ABSTRACT FROM AUTHOR]

The medical emergency of COVID-19 brought to the forefront mRNA vaccine technology where the mRNA vaccine candidates mRNA-1273 and BNT162b2 displayed superlative and more than 90% efficacy in protecting against SARS-CoV2 infections. Rare genetic disorders are rare individually, but collectively they are common and represent a medical emergency. In mRNA biotherapeutic technology, administration of a therapeutic protein-encoding mRNA-nanoparticle formulation allows for in vivo production of therapeutic proteins to functionally complement the protein functions lacking in rare disease patients. The platform nature of mRNA biotherapeutic technology propels rare disease drug discovery and, owing to the scalable and synthetic nature of mRNA manufacturing, empowers parallel product development using a universal production pipeline. This review focuses on the advantages of mRNA biotherapeutic technology over current therapies for rare diseases and provides summaries for the proof-of-concept preclinical studies performed to demonstrate the potential of mRNA biotherapeutic technology. Apart from preclinical studies, this review also spotlights the clinical trials currently being conducted for mRNA biotherapeutic candidates. Currently, seven mRNA biotherapeutic candidates have entered clinical trials for rare diseases, and of them, 3 candidates entered in the year 2023 alone. The rapid pace of clinical development promises a future where, as with mRNA vaccines for COVID-19, mRNA biotherapeutic technology would combat an emergency of rare genetic disorders. [ABSTRACT FROM AUTHOR]

Amid the growing challenge of antibiotic resistance on a global scale, there has been a notable resurgence in bacteriophage-based treatments, signaling a shift in our approach to managing infections. Bacteriophages (BPs), bacterial predators of nature, present a promising alternative for tackling infections caused by antibiotic-resistant pathogens. This review delves into the intricate relationship between bacteriophages and resistant bacteria, exploring various treatment strategies. Drawing upon both preclinical and clinical studies, the review highlights the effectiveness of bacteriophage therapy, particularly when integrated synergistically with conventional antibiotics. It discusses various treatment approaches for systemic and localized infections, demonstrating the adaptability of bacteriophage therapy across different clinical scenarios. Furthermore, the formulation and delivery of bacteriophages shed light on the various methods used to encapsulate and administer them effectively. It also acknowledges the challenge of bacterial resistance to bacteriophages and the ongoing efforts to overcome this hurdle. In addition, this review highlights the importance of the bacteriophage sensitivity profile (phagogram), which helps tailor treatment regimens to individual patients and specific pathogens. By surpassing the limitations of traditional antibiotics, bacteriophage-based therapies offer a personalized and potent solution against antibiotic resistance, promising to reshape the future of infectious disease management.

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE's risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients. [ABSTRACT FROM AUTHOR]

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE’s risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients.

Inflammation is a defense process triggered when the body faces assaults from pathogens, toxic substances, microbial infections, or when tissue is damaged. Immune and inflammatory disorders are common pathogenic pathways that lead to the progress of various chronic diseases, such as cancer and diabetes. The overproduction of cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, is an essential parameter in the clinical diagnosis of auto-inflammatory diseases. In this review, the effects of bee products have on inflammatory and autoimmune diseases are discussed with respect to the current literature. The databases of Google Scholar, PubMed, Science Direct, Sci-Finder and clinical trials were screened using different combinations of the following terms: “immunomodulatory”, “anti-inflammatory”, “bee products”, “honey”, “propolis”, “royal jelly”, “bee venom”, “bee pollen”, “bee bread”, “preclinical trials”, “clinical trials”, and “safety”. Honey bee products, including propolis, royal jelly, honey, bee venom, and bee pollen, or their bioactive chemical constituents like polyphenols, demonstrate interesting therapeutic potential in the regulation of inflammatory mediator production as per the increase of TNF-α, IL-1β, IL-6, Il-2, and Il-7, and the decrease of reactive oxygen species (ROS) production. Additionally, improvement in the immune response via activation of B and T lymphocyte cells, both in in vitro, in vivo and in clinical studies was reported. Thus, the biological properties of bee products as anti-inflammatory, immune protective, antioxidant, anti-apoptotic, and antimicrobial agents have prompted further clinical investigation.

Vegetables of the Allium genus, such as garlic (Allium sativum L.), onions, shallots, leaks, and chives, have been used for many years for food consumption and for medicinal purposes. Historical medical texts have indicated the therapeutic applications of garlic as an antitumor, laxative, diuretic, antibacterial and antifungal agent. Specifically, garlic's antitumor abilities have been traced back 3500 years as a chemotherapeutic agent used in Egypt. Other beneficial effects of garlic consumption include lowering blood pressure, blood cholesterol, sugar and lipids. The processing and aging of garlic result in the production of non-toxic organosulfur by-products. These sulfur-containing compounds, such as allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, alliin, S-allylcysteine, and S-allylmercaptocysteine, impact various stages of carcinogenesis. The anticancer mechanisms of action of these garlic-derived phytochemicals include altering mitochondrial permeability, inhibiting angiogenesis, enhancing antioxidative and proapoptotic properties, and regulating cell proliferation. All these effects of garlic's sulfur-compounds have been demonstrated in various human cancers. The intent of this literature research is to explore the potential of garlic-derived products and bioactive organosulfur compounds as cancer chemopreventive and chemotherapeutic agents. This investigation employs criteria for systematic review and critically analyzes published in vitro, in vivo and clinical studies. Concerns and limitations that have arisen in past studies regarding standards of measurement, bioavailability, and method of delivery are addressed. Overall, it is hoped that through this systematic and comprehensive review, future researchers can be acquainted with the updated data assembled on anticancer properties of garlic and its phytoconstituents. [ABSTRACT FROM AUTHOR]

Addiction is a behavioural disorder associated with proven deregulation of the functions of the CNS (in the dorsal striatum, globus pallidus, nucleus accumbens, hippocampus, thalamus, amygdala, orbitofrontal, and prefrontal cortex), which are also associated with functional changes in vital internal organs. In recent years, the application of cannabidiol (CBD), one of the cannabinoids without psychotropic activity, has become one of the options for the proposed treatment of addictions. The repeatedly described effects of cannabidiol, confirming the suppression of neurotoxic, behavioural, and other changes in both preclinical and clinical studies of addictions are considered to recommend further research for verification of the suitability of the indication of cannabidiol for the treatment of addictions. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a devastating, autosomal-dominant inherited, neurodegenerative disorder characterized by progressive motor deficits, cognitive impairments, and neuropsychiatric symptoms. It is caused by excessive cytosine-adenine-guanine (CAG) trinucleotide repeats within the huntingtin gene (HTT). Presently, therapeutic interventions capable of altering the trajectory of HD are lacking, while medications for abnormal movement and psychiatric symptoms are limited. Numerous pre-clinical and clinical studies have been conducted and are currently underway to test the efficacy of therapeutic approaches targeting some of these mechanisms with varying degrees of success. In this review, we update the latest advances on new promising molecular-based therapeutic strategies for this disorder, including DNA-targeting techniques such as zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9; post-transcriptional huntingtin-lowering approaches such as RNAi, antisense oligonucleotides, and small-molecule splicing modulators; and novel methods to clear the mHTT protein, such as proteolysis-targeting chimeras. We mainly focus on the ongoing clinical trials and the latest pre-clinical studies to explore the progress of emerging potential HD therapeutics., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (© 2024 Yangfan Cheng, Sirui Zhang, Huifang Shang, published by De Gruyter on behalf of Scholar Media Publishing.)

Background: Given the persistence and the worldwide shortage of organs from both the deceased and living donors for clinical transplantation, pig organs or tissues hold immense promises for the patients on the waiting list, and xenotransplantation is deemed as one of the solutions to the organ shortage crisis. Indeed, the emerging gene editing technologies, such as CRISPR/Cas9, have led to tremendous progress in the generation of genetically modified pigs to overcome many barriers associated. Method: We presented a description of the xenotransplantation regulations in China and the related products. Result: Several groups in China have successfully generated transgenic pigs with the elimination of immune rejection or coagulation‐related genes, and both pre‐clinical and clinical studies have been reported. However, the pre‐clinical evaluation and clinical application of porcine xenotransplantation raises ethical and regulatory considerations. Herein, in this review, we will summarize and discuss the progress in xenotransplantation in China and xenotransplantation‐related products from the regulatory perspective. Conclusion: There has been remarkable progress in both the genetically modified pigs and pre‐clinical studies in China, and China will be the first country to successfully fulfill the xenotransplantation from pig organ to human in the near future. [ABSTRACT FROM AUTHOR]

Chronic pelvic pain syndrome (CPPS) can be triggered by a various types of gynecological, gastrointestinal, urological, and musculoskeletal disorders. Recently, the role of the central nervous system has proven to be an integral part on the development of any chronic pain syndrome, including CPPS. However, owing to the complex and heterogeneous etiology and pathophysiology of CPPS, the establishment of effective therapeutic interventions remains challenging for both physicians and patients. Nonetheless, recent studies have pointed that medicinal plants and their secondary metabolites can be effectively used in CPPS therapy, besides contributing to restore the patients' quality of life and potentiate the conventional CPPS management. In this sense, this review aims to provide a careful overview on the biomedical data for the use of medicinal plants use and their secondary metabolites on CPPS management. [ABSTRACT FROM AUTHOR]

According to the World Health Organization estimates, approximately 10% of the world’s population is affected by depressive disorders. Furthermore, even in high-income countries, many people with depression are not treated, which can lead to serious health consequences and a global economic loss. Unfortunately, the current pharmacotherapy of depressive disorders is characterized by unsatisfactory efficacy and the therapeutic effect is accompanied by many side effects. For this reason, there is still ongoing worldwide research to find new antidepressant therapies. In recent years, many data have been shown that essential elements demonstrate the antidepressant action and increase the effect of antidepressants. In this paper we present the results from the preclinical and clinical studies published over the years which show the involvement of selenium and manganese in depressive disorders. In this article, the relationship between the amount of these microelements in a diet and depression is reviewed and what's more, the association among these elements in different biomaterial and their relations to depressive symptoms is presented. Additionally, we discuss the possible influence of selenium and manganese on modulating neurotransmitter system involved in depression.

Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE's risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients.

Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

Antiviral drug Kagocel is widely used in Russia for prevention and treatment of acute respiratory infection, influenza, and herpes. The drug belongs to the group of interferon inductors. The article contains the review and analytical evaluation of safety of antiviral drug Kagocel. Kagocel is registered in the Russian Federation and some CIS countries and refers to the group of interferon inducers. This is a chemical compound of carboxymethyl cellulose and low-molecular natural polyphenol gossypol common in cotton-plant (Gossypium spp.) which protects the plant from depredators and diseases. Authors pay a special attention to the analysis and generalization of data from preclinical and clinical studies including the control of related substances. Absence of free gossypol impurities guaranteed by highly sensitive and specific quality control methods. Preclinical studies data was analyzed and the results were presented with focus on reproductive safety of Kagocel® in immature and mature animals.. No negative effect on animals' reproductive function was revealed including spermatogenesis and generative function. No long-term product effect on reproductive system or next generations of animals was recorded both at therapeutic doses and at doses 10 times their exceeding. The safety of the drug demonstrated on data obtained from numerous clinical trials, including those involving children aged 2 years and older. Th is confirms the safety of antiviral drug Kagocel usage in clinical practice, including pediatrics. [ABSTRACT FROM AUTHOR]

In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of paclitaxel (Taxol ® ), while maximizing the proven antineoplastic activity of the drug against many solid tumors. Hence, different types of nanocarriers have been employed to improve the efficacy, safety, physicochemical properties and pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the unique drug that is marketed in three different nanoplatforms for its parenteral delivery: polymeric nanoparticles (Abraxane ® ), liposomes (Lipusu ® ), and polymeric micelles (Genexol ® , Nanoxel ® and Paclical ® ). Indeed, a fourth nanocarrier might be available soon, because phase III studies of Opaxio™, a polymeric-conjugated, are near completion. Furthermore, other several nanoformulations are currently in various stages of clinical trials. Therefore, it is only through the critical analysis of clinical evidence from these studies that we can get a more concrete idea of what has been achieved with pharmaceutical nanotechnology so far. This review attempts to summarize current information available regarding the clinical status and the physicochemical characteristic of different nanocarriers for paclitaxel delivery in cancer therapy. We present an overview of the preclinical and clinical data of these systems including their pharmacokinetics, dose and administration, adverse events and clinical efficacy. [ABSTRACT FROM AUTHOR]

Background. Anti-inflammatory, analgesic, anticonvulsant, and other effects have been attributed to cannabis, and so it has been widely used to treat several diseases. Objective. To assess the use and therapeutic effects of cannabinoid drugs and the cannabis plant in several diseases. Method. We carried out a narrative review of the literature that has reported the use of the cannabis plant (marijuana) and cannabinoid drugs (nabilone, cannabinol and dronabinol, among others). We conducted a search in Medline, Cochrane, SciELO and other web sites. Clinical, controlled, double-blind and randomized studies were included. The route of administration and the cannabinoid drugs used were assessed too. Results. Thirty-four studies were included. Nabilone was the cannabinoid drug more commonly used (12 studies), followed by delta-9-tetrahydrocannabinol (THC) (11 studies). It was also found that the marijuana plant and cannabinoid drugs were used to treat many symptoms or diseases. Two studies were reported for Gilles de la Tourette's syndrome. Discussion and conclusion. Many scientific studies on the marijuana plant and cannabinoid drugs conclude that these are not as effective as conventional medications and thus their benefits should be taken with caution. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors., (© 2023 Wiley Periodicals LLC.)

Introduction: Depression is one of the most frequently occurring psychiatric disorders worldwide, affecting 121 million worldwide. World Health Organization (WHO) estimates that it is the leading cause of disability and the fourth leading contributor to the "global burden of diseases"., Objective: Investigating and developing a drug with a novel benefit-risk profile is critical. Marine sources have been explored for their benefits as an alternative therapy for depression treatment. Numerous studies have shown that natural compounds containing peptides, alkaloids, polyphenols, diterpenes, glycosides, vitamins, and minerals from marine sources can potentially treat a wide range of disorders, including depression. Such phytoconstituents are known to reduce oxidative stress and neuroinflammation, regulate the synthesis or function of neurotransmitters such as glutamate and acetylcholinesterase, and aid in enhancing serotonin levels and nerve development., Methods: In this review study, a literature search was conducted using terms often used, including animal models of depression and their precise phases, marine sources, algae, sponges, and indole alkaloids. Additionally, databases were examined, including Scopus, Wiley, Elsevier, Google Scholar, and Web of Science. The Snowball technique was used to identify several articles about depression but correlated to marine sources in addition to database searches., Results: Current antidepressant medications have several negative side effects on the human body, including dry mouth, cardiovascular interference, gastrointestinal symptoms, genitourinary symptoms, hepatotoxicity, convulsions, and obesity. As a result, researchers can identify a wide range of potential targets for medications derived from marine sources. A combination of marinederived drugs and available treatments can be estimated to minimize the negative effects. So that these resources can be used as efficiently as possible, and various marine-derived substances can be studied for therapeutic efficacy., Conclusion: This review focuses on the preclinical and clinical findings of marine-derived compounds with antidepressant properties that alter behavioural parameters and biochemical abnormalities, as well as their mechanism of action and in-vivo potential., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell-penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored in in vivo studies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging. This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood-brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The lack of satisfactory results of alcohol dependence treatment force us to search for new directions of research. Recent studies concentrate on endocannabinoid transmission. The results show an interplay between the endocannabinoid and dopaminergic signaling in activation of the limbic reward system. The mechanisms leading to development of dependence are very complex and poorly recognized. Endogenous cannabinoids seem to have an important role in the functioning of this system, both directly and indirectly affecting the level of different neurotransmitters. The effect of alcohol on the endocannabinoid system is also complex and involves changes at the molecular level. Experimental studies have demonstrated an important role of the CB1 receptors in the neurochemical mechanism of alcohol consumption and its regulation. SR141716 (rimonabant), a CB1 receptor antagonist, significantly lowers voluntary alcohol intake and motivation for its consumption in various experimental studies. Very encouraging results of preclinical studies were not completely confirmed in the clinical studies. However, further clinical studies are still necessary [ABSTRACT FROM AUTHOR]

In recent times, focus on plant research has increased all over the world. Centella asiatica is an important medicinal herb that is widely used in the orient and is becoming popular in the West. Triterpenoid, saponins, the primary constituents of Centella asiatica are manly believed to be responsible for its wide therapeutic actions. Apart from wound healing, the herb is recommended for the treatment of various skin conditions such as leprosy, lupus, varicose ulcers, eczema, psoriasis, diarrhoea, fever, amenorrhea, diseases of the female genitourinary tract and also for relieving anxiety and improving cognition. The present review attempts to provide comprehensive information on pharmacology, mechanisms of action, various preclinical and clinical studies, safety precautions and current research prospects of the herb. At the same time, studies to evaluate the likelihood of interactions with drugs and herbs on simultaneous use, which is imperative for optimal and safe utilization of the herb, are discussed. [ABSTRACT FROM AUTHOR]

Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types. In models of stroke, the principal mechanism by which any improvement has been observed, has been attributed to the release of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however, issues still need to be addressed for use in human subjects. [ABSTRACT FROM AUTHOR]

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Alzheimer’s disease is the fourth largest cause of death for people over 65 years of age. Dementia of Alzheimer’s type is the commonest form of dementia, the other two forms being vascular dementia and mixed dementia. At present, the therapy of Alzheimer’s disease is aimed at improving both, cognitive and behavioural symptoms and thereby, quality of life for the patients.Since the discovery of Alzheimer’s disease by Alois Alzheimer, many pathological mechanisms have been proposed which led to the testing of various new treatments. Until recently the available drugs for the treatment of Alzheimer’s disease are cholinesterase inhibitors, which have limited success because these drugs improve cognitive functions only in mild dementia and cannot stop the process of neurodegeneration. Moreover, drugs of this category show gastrointestinal side effects. As the cells of central and peripheral nervous system cannot regenerate, newer strategies are aimed at preserving the surviving neurons by preventing their degeneration. NMDA-receptor-mediated glutamate excitotoxicity plays a major role in Aβ-induced neuronal death. Hence, it was thought that NMDA receptors could be a promising target for preventing the progression of Alzheimer’s disease. All the compounds synthesized initially in this category showed toxicity mainly because of their high affinity for NMDA receptors. Memantine (1-amino adamantane derivative), NMDA-receptor antagonist was reported to be effective therapeutically in Alzheimer’s disease. It was available in Germany as well as European Union and has been approved for moderate to severe dementia in United States of America recently. It is an uncompetitive, moderate affinity antagonist of NMDA receptors that inhibits the pathological functions of NMDA receptors while physiological processes in learning and memory are unaffected.Memantine is also reported to have beneficial effects in other CNS disorders viz., Parkinson’s disease (PD), stroke, epilepsy, CNS trauma, amyotrophic lateral sclerosis (ALS), drug dependence and chronic pain.Mechanisms of neuroprotection, preclinical and clinical evidence for effectiveness of memantine have been provided. Pharmacology and pharmacokinetics of memantine and other NMDA-receptor antagonists in comparison with currently approved drugs for dementia treatment have been discussed. The focus is on ‘glutamate excitotoxicity’ and glutamate receptors as drug target. Various other novel strategies for the treatment of dementia of neurodegenerative disorders have also been discussed. [Copyright &y& Elsevier]

Inflammation is a defense process triggered when the body faces assaults from pathogens, toxic substances, microbial infections, or when tissue is damaged. Immune and inflammatory disorders are common pathogenic pathways that lead to the progress of various chronic diseases, such as cancer and diabetes. The overproduction of cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, is an essential parameter in the clinical diagnosis of auto-inflammatory diseases. In this review, the effects of bee products have on inflammatory and autoimmune diseases are discussed with respect to the current literature. The databases of Google Scholar, PubMed, Science Direct, Sci-Finder and clinical trials were screened using different combinations of the following terms: "immunomodulatory", "anti-inflammatory", "bee products", "honey", "propolis", "royal jelly", "bee venom", "bee pollen", "bee bread", "preclinical trials", "clinical trials", and "safety". Honey bee products, including propolis, royal jelly, honey, bee venom, and bee pollen, or their bioactive chemical constituents like polyphenols, demonstrate interesting therapeutic potential in the regulation of inflammatory mediator production as per the increase of TNF-α, IL-1β, IL-6, Il-2, and Il-7, and the decrease of reactive oxygen species (ROS) production. Additionally, improvement in the immune response via activation of B and T lymphocyte cells, both in in vitro, in vivo and in clinical studies was reported. Thus, the biological properties of bee products as anti-inflammatory, immune protective, antioxidant, anti-apoptotic, and antimicrobial agents have prompted further clinical investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 El-Seedi, Eid, Abd El-Wahed, Rateb, Afifi, Algethami, Zhao, Al Naggar, Alsharif, Tahir, Xu, Wang and Khalifa.)

Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated. [ABSTRACT FROM AUTHOR]

A large body of research has shown the presence of a complex pathway of communications between the gut and the brain. It is now recognized that, through this pathway, the microbiota can influence brain homeostasis and plasticity under normal and pathological conditions. This review aims at providing an overview of preclinical and clinical pieces of evidence supporting the possible role of gut-brain axis modulation in physiological aging, in a neurodevelopmental disorder, the autism spectrum disorders and in a substance abuse disorder, the alcohol addiction. Since the normalization of gut flora can prevent changes in the behavior, we postulate that the gutbrain axis might represent a possible target for pharmacological and dietary strategies aimed at improving not only intestinal but also mental health. The present review also reports some regulatory considerations regarding the use of probiotics, illustrating the most debated issues about the possibility of considering probiotics not only as a food supplement but also as a "full" medicinal product., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Treatment of patients suffering from major depression could be highly challenging for psychiatrists. Intractability as well as relapse is commonly seen among these patients, leading to functional impairment and poor quality of life. The present review discusses some of the novel investigational drugs that are under pre-clinical or clinical phases in the treatment of major depression. Areas covered: Molecules belonging to different classes such as triple reuptake inhibitors, opioid receptors, ionotropic and metabotropic glutamate receptors, and neurotrophin in the treatment of major depression are covered in this article. Expert opinion: Although the historical discovery of earlier antidepressant molecules (iproniazid and imipramine) is through serendipitous discovery, the present research focuses on discovering novel molecules based on our current pathophysiological knowledge of the disease condition. The fast-acting antidepressant property of N-methyl-d-aspartate (NMDA) receptor molecules, including ketamine is an exciting area of research. Other drug molecules such as amitifadine (triple reuptake inhibitor), ALKS-5461 (kappa receptor antagonist and mu opioidergic receptor agonist), rapastinel (NMDA glutamatergic receptor modulator) are under Phase-III clinical trials and could be approved in the near future for the treatment of major depression.