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Diabetes is a major global health crisis, affecting millions of people worldwide and necessitating the search for effective and safe treatments, leading to various complications, including liver damage. This study investigated the hepatoprotective and antidiabetic properties of cryogenically pulverized Turkish propolis water extracts (WBTP) in streptozotocin-induced diabetic rats. Propolis samples were collected from the West Black Sea Region of Turkey and prepared as -80 °C (PP-80) and -196 °C (PP-196) water extracts. Thirty male Wistar albino rats were divided into five groups: normal control, diabetic control, diabetic + PP-80 (250 mg/kg), diabetic + PP-196 (250 mg/kg), and diabetic + metformin (250 mg/kg). After 35 days of treatment, various parameters were evaluated, including body weight, blood glucose, glycated hemoglobin (HbA1c), serum biochemistry, antioxidant enzyme activities, and histopathology of the pancreas. The results showed that WBTP extracts, especially PP-80, significantly improved body weight and reduced blood glucose and HbA1c levels. Analysis of lipid profiles revealed improvements in HDL, LDL, triglycerides, and total cholesterol levels with WBTP treatment. The antioxidant defense systems were also enhanced in the WBTP-treated groups. Histopathological examination revealed that WBTP extracts mitigated pancreatic tissue damage in the diabetic rats. In conclusion, the WBTP extracts possess hepatoprotective and antidiabetic properties, suggesting a promising avenue for further research. It emphasizes the importance of addressing both diabetes and hepatopathologies concurrently and highlights WBTP extracts as natural and potentially safer alternatives to synthetic antidiabetic drugs. Specifically, PP-80 extracts demonstrate robust effects in managing diabetes and associated liver complications in streptozotocin-induced diabetic rats, indicating their therapeutic potential. [Display omitted] • Cryogenically pulverized Turkish propolis water extracts (WBTP) were investigated for their hepatoprotective and antidiabetic properties. • WBTP extracts, particularly PP-80, significantly improved body weight and reduced blood glucose and HbA1c levels in streptozotocin-induced diabetic rats. • WBTP treatment improved lipid profiles and enhanced antioxidant defense systems. • Histopathological examination revealed mitigation of pancreatic tissue damage in diabetic rats. • WBTP extracts demonstrate potential as natural alternatives to synthetic antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Pharmaceuticals can directly inhibit the growth of gut bacteria, but the degree to which such interactions manifest in complex community settings is an open question. Here, we compared the effects of 30 drugs on a 32-species synthetic community with their effects on each community member in isolation. While most individual drug-species interactions remained the same in the community context, communal behaviors emerged in 26% of all tested cases. Cross-protection during which drug-sensitive species were protected in community was 6 times more frequent than cross-sensitization, the converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that the resilience of microbial communities can collapse when perturbations get stronger. By metabolically profiling drug-treated communities, we showed that both drug biotransformation and bioaccumulation contribute mechanistically to communal protection. As a proof of principle, we molecularly dissected a prominent case: species expressing specific nitroreductases degraded niclosamide, thereby protecting both themselves and sensitive community members. [Display omitted] • Bacteria can be protected from and sensitized to drugs in a community context • Cross-protection and community resilience dissipate at high drug concentrations • Drug biotransformation and bioaccumulation can partially explain communal protection • Enzyme specificity and expression dictate detoxification of nitroaromatic drugs A comparison of the effects of pharmaceuticals on different gut bacterial species when grown alone or as part of a community shows that complex microbial communities can protect, and less frequently sensitize, community members to the treatment. Both drug biotransformation and bioaccumulation are key to community protection, which can be overwhelmed at high drug concentrations. [ABSTRACT FROM AUTHOR]

Indolizines and imidazo[1,2‐a]pyridines are commonly found in natural products, synthetic drugs, and bioactive molecules. These two types of derivatives possess good antibacterial, antiparasitic, anticancer activities, and so on. The functionalization of indolizines and imidazo[1,2‐a]pyridines has always been a hot topic in organic chemistry research and has made significant progress. In recent years, our group has been dedicated to developing diverse synthetic methods for the preparation of such important compounds. 1) We have developed diverse C−H functionalization reactions for efficient modification of the parent indolizines and imidazo[1,2‐a]pyridines. 2) A variety of cycloaddition reactions were established for the construction of indolizine and imidazo[1,2‐a]pyridine derivatives from simple raw materials. 3) We have developed intriguing deconstruction‐functionalization reactions of indolizines, enabling the reorganization of heterocyclic frameworks. This paper outlines our group's latest advancements in constructing structurally diverse indolizine and imidazo[1,2‐a]pyridine derivatives. We hope that this work will offer valuable insights and inspiration for the ongoing research in the field of N‐heterocyclic compounds. [ABSTRACT FROM AUTHOR]

Simple Summary: Mortalin is a heat shock protein 70 stress chaperone family member with variable subcellular localization in normal and cancer cells. It is an essential protein with multiple functions that support and promote proliferation, endorsed by its enriched expression in various cancers. Due to its prime involvement in stress adaptation and carcinogenesis, regulating Mortalin expression and function is a viable therapeutic avenue. Upregulation of stress chaperone Mortalin has been closely linked to the malignant transformation of cells, tumorigenesis, the progression of tumors to highly aggressive stages, metastasis, drug resistance, and relapse. Various in vitro and in vivo assays have provided evidence of the critical role of Mortalin upregulation in promoting cancer cell characteristics, including proliferation, migration, invasion, and the inhibition of apoptosis, a consistent feature of most cancers. Given its critical role in several steps in oncogenesis and multi-modes of action, Mortalin presents a promising target for cancer therapy. Consequently, Mortalin inhibitors are emerging as potential anti-cancer drugs. In this review, we discuss various inhibitors of Mortalin (peptides, small RNAs, natural and synthetic compounds, and antibodies), elucidating their anti-cancer potentials. [ABSTRACT FROM AUTHOR]

AbstractThe incidence of Alzheimer’s is increasing and poses a significant social and economic burden. The pathogenesis involved in the expansion of AD includes neuronal oxidative damage, tau phosphorylation, amyloid beta aggregation, neuroinflammation, etc. Despite enormous efforts, there is currently no effective treatment or cure for this condition in the allopathic system. Marine compounds are appealing options and have a strong neuroprotective impact. Marine-derived compounds from sponges, algae, and marine invertebrates can be used for neuroprotection, with fewer adverse effects than synthetic drugs. Various compounds such as bryostatin-1, docosahexaenoic acid, spirolides, and astaxanthin, GV-971, have demonstrated outstanding activity and bioavailability. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous character of functional gastrointestinal disorders, recently renamed into disorders of gut‐brain interaction, makes finding effective treatment options challenging. Compared to synthetic drugs, phytotherapy can have broader pharmacological effects and is often better tolerated. This study aimed to investigate the effect of peppermint oil and caraway oil (POCO) on gastric function and symptom levels in 32 healthy subjects in a single‐blinded, placebo‐controlled, randomized, parallel design. Methods: Gastric emptying rate was assessed using a 13C‐breath test. Intragastric pressure was measured using high‐resolution manometry in fasted state and during intragastric infusion of a nutrient drink (350 mL or until full satiation). GI symptoms were rated on a 100 mm VAS. Data were analyzed using linear mixed models. Key Results: POCO had no effect on intragastric pressure in fasted or fed state (p > 0.08 for all). No significant differences in gastric emptying rate were observed (p = 0.54). In the fasted state, a stronger increase in hunger and decrease in satiety were observed following POCO (p = 0.016 and p = 0.008, respectively). No differences in hunger and satiety were observed in the fed state (p > 0.31 for all). POCO induced less epigastric burning, bloating, and fullness (p < 0.05 for all). Conclusions: Acute POCO administration did not affect gastric function in healthy subjects, but increased fasted hunger ratings. The effects of POCO on gastric function and hunger sensations in patients with disorders of gut‐brain interaction, and the contribution to symptom improvement, needs to be elucidated in future studies. [ABSTRACT FROM AUTHOR]

Long COVID (LC) refers to a condition characterized by a variety of lingering symptoms that persist for more than 4 to 12 weeks following the initial acute SARS-CoV-2 infection. Recent research has suggested that the FOXP4 gene could potentially be a significant factor contributing to LC. Owing to that, this study investigates FOXP4’s role in LC by analyzing public datasets to understand its evolution and expression in diverse human populations and searching for drugs to reduce LC symptoms. Population genetic analysis of FOXP4 across human populations unmasks distinct genetic diversity patterns and positive selection signatures, suggesting potential population-specific susceptibilities to conditions like LC. Further, we also observed that FOXP4 experiences high expression during LC. To identify potential inhibitors, drug screening analysis identifies synthetic drugs like Glisoxepide, and natural compounds Kapurimycin A3 produced from Streptomyces sp, and Cucurbitacin B from Begonia nantoensis as promising candidates. Overall, our research contributes to understanding how FOXP4 may serve as a therapeutic target for mitigating the impact of LC. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the impact of different patterns of healthcare delivery on remission of rheumatoid arthritis (RA) patients treated with targeted therapies during the first wave (2020) and second/third waves (2021) of the pandemic compared to the pre-pandemic period (2019). Methods: In this observational real-life study, data from RA patients treated with biologic or targeted synthetic drugs were extracted from a longitudinal registry. Clinical Disease Activity Index (CDAI) was analyzed in the same period from the 22nd of February to the 18th of May for three consecutive years. These three periods were characterized by different patterns of healthcare delivery: (1) before the pandemic (2019) only in-person visits, (2) during the first wave (2020) both in-person visits and telehealth, and (3) during the second/third waves (2021) only in-person visits. A generalized linear model with the binomial error was fitted to evaluate the difference in the proportion of patients in CDAI remission. Quantile regression was used to compare the median of CDAI in difficult-to-treat (D2T) patients. Results: In the three periods, we included 407, 450, and 540 RA patients respectively. The percentages of patients in CDAI remission were similar in the three periods (prevalence ratio 1.07, p value 0.423 between 2020 and 2019, and 1.01, p-value 0.934 between 2021 and 2019). The CDAI remission rate was 40.55% (N = 163), 43.18% (N = 155) and 40.82% (N = 220) in 2019, 2020 and 2021, respectively. Among our cohort of D2T patients, CDAI remission was similar across the three periods (N = 30, 22.22%; N = 27, 23.68%; and N = 34, 21.52% respectively). Conclusion: Although the pandemic has imposed changes in our healthcare delivery, these different strategies seem to be effective in ensuring satisfactory management of RA treated with targeted therapies. The approaches modulated in the context of the different periods have been a feasible compensation for ensuring disease control even in D2T patients. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoid receptor agonists (SCRAs) are a class of synthetic drugs that mimic and greatly surpass the effect of recreational cannabis. Acute SCRA intoxications are in general difficult to assess due to the large number of compounds involved, differing widely in both chemical structure and pharmacological properties. The rapid pace of emergence of unknown SCRAs hampers on one hand the timely availability of methods for identification and quantification to confirm and estimate the extent of the SCRA intoxication. On the other hand, lack of knowledge about the harm potential of emerging SCRAs hampers adequate interpretation of serum concentrations in intoxication cases. In the present study, a novel comparative measure for SCRA intoxications was evaluated, focusing on the cannabinoid activity (versus serum concentrations), which can be measured in serum extracts with an untargeted bioassay assessing ex vivo CB1 activity. Application of this principle to a series of SCRA intoxication cases (n = 48) allowed for the determination of activity equivalents, practically entailing a conversion from different SCRA serum concentrations to a JWH-018 equivalent. This allowed for the interpretation of both mono- (n = 34) and poly-SCRA (n = 14) intoxications, based on the intrinsic potential of the present serum levels to exert cannabinoid activity (cf. pharmacological/toxicological properties). A non-distinctive toxidrome was confirmed, showing no relation to CB1 activity. The JWH-018 equivalent was partly related to the poison severity score (PSS) and causality of the clinical intoxication elicited by the SCRA. Altogether, this equivalent concept allows to comparatively and timely interpret (poly-)SCRA intoxications based on CB1 activity. [ABSTRACT FROM AUTHOR]

• The Zulus engage in complementary and alternative medicine through a traditional healing system known as izangoma. • The first review of the antidiabetic medicinal plants commonly used by the Zulus of Kwazulu-Natal province of South Africa. • The list includes local and botanical names, the parts commonly used, isolated bioactive principles and their reported mechanisms of action. • 38 plants covering 20 families were identified with Asteraceae accounting for 34.2% and the leaves was the most used plant part (50 %). • 29 have been scientifically validated while nine lack scientific verification. Diabetes mellitus is a chronic metabolic disorder that affects millions of people worldwide. Its conventional management involves diet modification, exercise, and majorly the use of synthetic drugs, which may be ineffective, have adverse effects, and of relatively expensive costs. To mitigate the downsides of the available treatments, alternative therapies from medicinal plants are commonly sought by different ethnic groups including the Zulus. This paper appraised the antidiabetic plants used by the Zulus, their local and botanical names, the parts commonly used, isolated bioactive principles and their reported mechanisms of action. 38 plants covering 20 families were identified with Asteraceae accounting for 31.57 % and the leaves was the most used plant part (50 %). Out of the 38 plants identified, 28 have been scientifically validated using in vitro/in vivo models but identifying the plant with the most potent hypoglycemic activity remains challenging due to variations in biological activities. Important antidiabetic agents such as quercetin, squalene, kaempferol, isomukaadial acetate, phytol, sitosterol, apigenin, catechin and their derivates have been isolated and characterized from the verified plants though, more scientific exploration is required to develop these principles into valuable antidiabetic medications with establish mechanism of action. Scientists therefore needs to beam their searchlight and dedicate resources to the rich botanicals of the Zulu land with the view to providing indigenous solutions that can be incorporated into modern medicine for diabetes management. [ABSTRACT FROM AUTHOR]

• A concise overview on the isolated bioactive compounds from different Annona plant part. • Annona extracts have been shown to exert significant biological and pharmacological activities of isolated compounds with mechanism of its action. • On the current preclinical evidence an association between bioactive component intake with a special focus on human chronic disease prevention. The use of plant derived bioactive substances as a key therapeutic agent to treat various diseases has gained great impetus recently. Annona fruits are currently gaining attention from those who are interested in eating foods that promote health because of its phytochemical composition, whose actions have not before been investigated. A comprehensive search was conducted on scientific databases like Google Scholar, PubMed, Science Direct, Scopus etc to retrieve the relevant literature on Annona species include Annona squamosa, Annona muricata, Annona reticulata, Annona glabra, Annona crassiflora, Annona cherimola, Annona montana, Annona purpurea, Annona senegalensis, Annona dioica and Annona atemoya , their bioactive compounds, biological activity, pharmacology and mechanism from January 2002 to February 2024. According to the available literature data bioactive phytocompound have proven to be a potential alternative to synthetic drugs especially because of their antioxidant, antibacterial and in vitro anticancer properties. This review aims to provide up-to-date information on Annona genus with mode of action on various disease. The literature accessible on this plant species was systematically analysed to extract evidence regarding its phytochemicals, including phenolic, ascorbic acid, fatty acids, essential oils, alkaloids etc. Moreover, the considerable data will be useful for pharmaceutical researchers and other industries looking for up-to-date understandings. Specifically, we provide a concise overview on the isolated bioactive compounds from different Annona part and occurrence of the main classes of compounds as well as on the current preclinical evidence an association between bioactive component intake with a special focus on human chronic disease prevention like neurodegenerative, anti-inflammatory, hyperglycaemic and cancer. Additional investigations are necessary to uncover the underlying mechanisms of its actions and conduct clinical trials to verify its effectiveness and safety in humans. [ABSTRACT FROM AUTHOR]

[Display omitted] Hollow block copolymer particles called polymer vesicles (polymersomes) serve as versatile containers for compartmentalization in synthetic biology and drug delivery. Recently, there has been growing interest in using polymersomes as colloidal building blocks for creating higher-order clustered structures. Most reports thus far rely on the use of DNA base-pairing interactions to "glue" polymersomes with other colloidal components. In this study, we present two alternative electrostatically driven approaches to assemble polymersomes and model colloids (micelles) into hybrid clusters. The first approach uses pH to manipulate electrostatic interactions and effectively control the clustering extent of micellar subunits on polymersomes, while the second approach relies on the hydrolysis of an acid trigger, glucono delta-lactone (GDL), to introduce temporal control over clustering. We envisage our approaches and structures reported herein will help inspire the creation of new prospects for materials science and biomedical applications. [ABSTRACT FROM AUTHOR]

Dyslipidaemia describes the condition of abnormal lipid levels in a person's bloodstream. Since the 1980s, statin medications have been used to treat dyslipidaemia and other comorbidities, such as stroke risk and atherosclerosis. Statin medications were initially synthesised from fungal metabolites, but many synthetic statin drugs have been manufactured since then. Statin medication is quite effective in reducing total cholesterol levels in the bloodstream, but it has limitations. Due to their poor water solubility, statin drugs possess poor oral bioavailability, which hinders their therapeutic efficacy. Nanoparticle drug delivery technology has been shown to improve the pharmacokinetic profiles of many drug classes, and statins have great potential to benefit from this. This paper reviewed the currently available literature on nanoparticle statin medication and evaluated the possible improvements that can be made to the pharmacokinetic profile and efficacy of conventional statin medication. It was found that the oral bioavailability of nanoparticle medication consistently outperformed conventional medication by up to 400% in some cases. Substantial improvements in time to peak plasma concentration and plasma concentration peaks were also found, and increased periods in circulation before excretion were shown. It was concluded that nanoparticle technology has the potential to completely replace conventional statin medication as it offers more significant benefits with minimal drawbacks. Upon further study and development, the manufacture of nanoparticle statin medication should become feasible enough for large-scale application, which will significantly benefit patients and unburden healthcare systems. [ABSTRACT FROM AUTHOR]

The current study investigates the antihyperglycemic potential of Mimusops elengi fruit extract in streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus, a chronic metabolic disorder, disrupts carbohydrate, fat, and protein metabolism due to impaired insulin function. With the rising prevalence of diabetes and the limitations of synthetic drugs, particularly their side effects and high cost in developing countries there is growing interest in alternative treatments, including plantbased therapies. Mimusops elengi, traditionally used for various medicinal purposes was tested for its ability to regulate blood glucose levels and improve metabolic health. The study used 25 male Sprague-Dawley rats divided into five groups: normal control, diabetic control, standard group treated with metformin (10 mg/kg) and two treatment groups receiving low (200 mg/kg) and high (400 mg/kg) doses of Mimusops elengi extract. Diabetes was induced using a single intraperitoneal injection of STZ (40 mg/kg) and the treatments were administered orally for 15 days. Blood glucose levels and body weight were monitored throughout the study and pancreatic tissue was examined histologically. Results revealed a significant reduction in blood glucose levels in rats treated with Mimusops elengi, with both the 200 mg/kg and 400 mg/kg doses demonstrating dosedependent hypoglycemic effects. The 400 mg/kg dose showed efficacy comparable to metformin. Additionally, Mimusops elengi treatment mitigated the weight loss typically observed in diabetic rats, suggesting improved metabolic function. Histopathological examination indicate the progressive improvement of pancreatic architecture with increased treatment dosing, suggesting a dose-dependent protective or restorative effect on pancreatic tissue in the diabetic rats. In conclusion, Mimusops elengi significantly reduced hyperglycemia and improved metabolic health in diabetic rats, making it a promising candidate for further investigation as a natural treatment for diabetes. Future research should focus on elucidating its mechanisms of action and evaluating its clinical potential in human trials. [ABSTRACT FROM AUTHOR]

Many of the existing antimicrobial agents are showing ineffectiveness against the pathogenic microbes due to the resistance of microbes towards them. But apart from the synthetic drugs, many herbs are found to be effective in the inhibition of these microbes and serve as potent anti-microbial agents. In this study, the methanolic extract of Grewia asiatica leaves was evaluated against the fungus i.e., Candida albicans and Trichophyton rubrum. The extract used to compare with the standard drug i.e., Amphoterecin. The extract at the concentration of 62.5µg/well showed the lowest inhibition and on increasing the concentration of extraction inhibition zone increased and the constant zone of inhibition found from 125-1000 µg/well in case of Candida albicans. The leaf extract of Grewia asiatica also showed the inhibition of the fungus Trichophyton rubrum. On increasing the extract concentration, the zone of inhibition also increased. The maximum inhibition showed in concentration of 1000 µg/well. [ABSTRACT FROM AUTHOR]

Diabetes, a global health concern, poses increasing mortality risks. The pathogenesis of diabetes involves multiple mechanisms, with oxidative stress being one of the key contributors. As synthetic drugs have various side effects, which can be minimized by using herbal plants. This study focuses on the In vitro antioxidant potential, α-amylase inhibition potential, identification of bioactive compounds, and hub genes in diabetes treatment mechanism by using C. tinctorius Extraction of C. tinctorious lead and flower was performed using different solvents (Distilled water, methanol, chloroform, and Dimethyl ether). After extraction different concentrations range from 25–200 mg/mL) was made and checked against activities. The antioxidant potential was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic contents (TPC), and total antioxidant capacity (TAC) assays, while antidiabetic activity was evaluated through α-amylase inhibition assay. Phytochemicals was identified by GC–MS analysis, followed by ADMET screening and network pharmacology analysis using Swiss Target Prediction, Gene Card, DesGeNet, DAVID, STRING, Cytoscape, and drug revitalization databases. Results revealed positive correlations with DPPH, TAC, and TPC. Methanol extract exhibited the highest inhibitory concentration. Screening of 46 compounds was performed by studying their pharmacokinetic properties which revealed 9 compounds effective against 204 diabetes targets. Moreover, their network analysis identified four hub genes, including AKT1, JUN, EGFR, and MMP9. These genes found highly associated with drugs like Colchicine and Serotobenine. Revitalization analysis also highlighted four genes (EGFR, PTGS2, AKT1, and MMP9) strongly correlated with FDA-approved drugs. The study suggests C. tinctorius methanol extract is a potential source for novel drugs. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids are a rapidly evolving, diverse class of new psychoactive substances. Synthetic cannabinoid use results in a higher likelihood of adverse events and hospitalization when compared to cannabis use. The mechanisms behind synthetic cannabinoid toxicity remain elusive. Furthermore, poly-substance use may be a significant contributing factor in many cases. This scoping review aimed to identify the key characteristics of synthetic cannabinoid co-exposure cases and discuss the potential implications of poly-substance use in humans. There were 278 human cases involving 64 different synthetic cannabinoids extracted from the databases. Cases involved a total of 840 individual co-exposures, with an average of four substances involved in each case. The most common co-exposures were alcohol (11.4%), opioids (11.2%), and cannabis (11.1%). When analyzed by case outcome, co-exposure to either antipsychotics/antidepressants, alcohol, or tobacco were significantly associated with mortality as an outcome (p < 0.05). Drug-use history (63.4%), mental illness (23.7%), and hypertensive and atherosclerotic cardiovascular disease (20.1%) were prevalent patient histories in the case cohort. There are several potential pharmacodynamic and pharmacokinetic interactions between co-exposure drugs and synthetic cannabinoids that could worsen clinical presentation and toxicity in synthetic cannabinoid users. Individuals with substance-use disorders or psychiatric illness would be especially vulnerable to these multi-drug interactions. Further research into these complex exposures is needed for the successful prevention and treatment of synthetic cannabinoid-related harms. [ABSTRACT FROM AUTHOR]

Motivation Retrosynthesis identifies available precursor molecules for various and novel compounds. With the advancements and practicality of language models, Transformer-based models have increasingly been used to automate this process. However, many existing methods struggle to efficiently capture reaction transformation information, limiting the accuracy and applicability of their predictions. Results We introduce RetroCaptioner, an advanced end-to-end, Transformer-based framework featuring a Contrastive Reaction Center Captioner. This captioner guides the training of dual-view attention models using a contrastive learning approach. It leverages learned molecular graph representations to capture chemically plausible constraints within a single-step learning process. We integrate the single-encoder, dual-encoder, and encoder–decoder paradigms to effectively fuse information from the sequence and graph representations of molecules. This involves modifying the Transformer encoder into a uni-view sequence encoder and a dual-view module. Furthermore, we enhance the captioning of atomic correspondence between SMILES and graphs. Our proposed method, RetroCaptioner, achieved outstanding performance with 67.2 % in top-1 and 93.4 % in top-10 exact matched accuracy on the USPTO-50k dataset, alongside an exceptional SMILES validity score of 99.4 % ⁠. In addition, RetroCaptioner has demonstrated its reliability in generating synthetic routes for the drug protokylol. Availability and implementation The code and data are available at https://github.com/guofei-tju/RetroCaptioner. [ABSTRACT FROM AUTHOR]

Purpose: The original aim of the study was to determine, in a double-blind 3-arm crossover human trial (n = 7), the effect of supplemental levels of iron (25 mg) and zinc (30 mg) on β-carotene (synthetic) bioavailability (10 h postprandial). However, despite the high dose of supplemental β-carotene (15 mg) consumed with the high fat (18 g), dairy-based breakfast test meal, there was a negligible postprandial response in plasma and triglyceride rich fraction β-carotene concentrations. We then systematically investigated the possible reasons for this low bioavailability of β-carotene. Methods: We determined (1) if the supplemental β-carotene could be micellised and absorbed by epithelial cells, using a Caco-2 cell model, (2) if the fat from the test meal was sufficiently bioavailable to facilitate β-carotene bioavailability, (3) the extent to which the β-carotene could have been metabolised and converted to retinoic acid/retinol and (4) the effect of the test meal matrix on the β-carotene bioaccessibility (in vitro digestion) and Caco-2 cellular uptake. Results: We found that (1) The supplemental β-carotene could be micellised and absorbed by epithelial cells, (2) the postprandial plasma triacylglycerol response was substantial (approximately 75–100 mg dL−1 over 10 h), indicating sufficient lipid bioavailability to ensure β-carotene absorption, (3) the high fat content of the meal (approximately 18 g) could have resulted in increased β-carotene metabolism, (4) β-carotene bioaccessibility from the dairy-based test meal was sixfold lower (p < 0.05) than when digested with olive oil. Conclusion: The low β-carotene bioavailability is probably due to a combination of the metabolism of β-carotene to retinol by BCMO1 and interactions of β-carotene with the food matrix, decreasing the bioaccessibility. Trail registration: The human trail was retrospectively registered (ClinicalTrail.gov ID: NCT05840848). [ABSTRACT FROM AUTHOR]

Objectives: This systematic review and meta‐analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. Materials and methods: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta‐analysis. Results: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3–1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667–1.360; p = 0.789; I2 = 73.271) efficacy. Conclusions: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has thrust RNA as a platform for drug development into the spotlight. However, identifying promising drug candidates is challenging. With advances in synthetic biology and artificial intelligence (AI) models, we can overcome this hurdle, transforming drug development and ushering in a new era in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

The article examines the relationship between biologic treatments for psoriasis and the risk of developing depression, based on a retrospective analysis of U.S. administrative claims data. Topics include the reduced incidence of depression among patients using biologics compared to conventional treatments, the relative risk reduction associated with different classes of biologics, and the implications of these findings for future treatment strategies.

Background: Anxiety transcends a natural emotion, evolving into a pathological condition with the potential to trigger cascading cardiovascular and psychiatric disorders. Although conventional allopathic medicine offers treatment options, concerns regarding their side effects and long-term efficacy remain prevalent. Medicinal plants contain natural compounds that may be promising sources of therapeutic drugs. Aims and Objectives: This study aims to compare the anxiolytic potential of ethanolic and aqueous extracts of Ocimum sanctum (OS). The growing appeal of plant-based therapies for anxiety stems from perceived advantages in safety and tolerability compared to synthetic drugs. Materials and Methods: The anxiolytic activity of aqueous and ethanolic extract of OS is evaluated with an elevated plus maze test. A total of 36 Wistar albino rats (150-200 g) were used and randomly divided into six groups of six animals each. The effects of the test drug at different doses, 100 and 200 mg/kg, were compared with the standard anxiolytic drug diazepam at 2 mg/kg body weight and the control group using distilled water at 0.5 mL/kg body weight. Results: The behavioral changes suggested reduced anxiety and openarm exploration in plus-maze indicates reduced anxiety in animals treated with OS extracts. The changes are significantly (P < 0.001) comparable with the standard drug diazepam. Conclusion: The ethanolic extracts of OS are more significant than aqueous extracts for evaluating anti-anxiety activity in a dose-dependent manner. In addition, ethanolic extracts are more likely to contain a wider range of bioactive compounds, which are thought to be responsible for the anti-anxiety effects of OS. [ABSTRACT FROM AUTHOR]

Breast cancer remains the most prevalent malignancy among women globally, presenting significant challenges in therapeutic strategies due to tumor heterogeneity, drug resistance, and adverse side effects. Recent advances in targeted therapies, particularly antibody-drug conjugates (ADCs), have shown promise in addressing these challenges by selectively targeting tumor cells while sparing normal tissues. This study provides a comprehensive analysis of two innovative ADCs targeting HER2 and Trop-2, which are critical markers in various breast cancer subtypes. These conjugates combine potent cytotoxic drugs with specific antibodies, leveraging the antigens' differential expression to enhance therapeutic efficacy and reduce systemic toxicity. Our comparative analysis highlights the clinical applications, efficacy, and safety profiles of these ADCs, drawing on data from recent clinical trials. In addition, the paper discusses the potential of these ADCs in treating other types of cancers where HER2 and Trop-2 are expressed, as well as the toxicity risks associated with targeting these antigens in normal cells. Additionally, the paper discusses novel synthetic drugs that show potential in preclinical models, focusing on their mechanisms of action and therapeutic advantages over traditional chemotherapy. The findings underscore the transformative impact of targeted ADCs in breast cancer treatment, noting significant advancements in patient outcomes and management of side effects. However, ongoing issues such as resistance mechanisms and long-term safety remain challenges. The conclusion offers a forward-looking perspective on potential improvements and the future trajectory of ADC research. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks. [ABSTRACT FROM AUTHOR]

Aim: This study sought to assess hepatitis B virus (HBV) serology and the incidence of HBV reactivation (HBVr) in rheumatology patients with resolved hepatitis B infection (HBsAg negative and HBcAb positive) who were undergoing treatment with biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Material and Method: Data from rheumatology patients treated with b/tsDMARDs were retrospectively reviewed from the electronic records. The demographic data, the anti-rheumatic drugs used, and the hepatitis serologies (HBsAg, anti-HBc IgG, anti-HBs, and anti-HCV) of the patients were analyzed. Results: The study included a total of 316 patients, of whom 217 (68.7%) were diagnosed with ankylosing spondylitis, 74 (23.4%) with rheumatoid arthritis, and 25 (7.9%) with psoriatic arthritis. Evaluation of the patients' viral serologies revealed that four (1.2%) were HBsAg positive, and 18 (5.7%) were HBsAg negative and HBcAb positive. Anti-HCV positivity was observed in one. Conclusion: The rate of resolved hepatitis B infection is relatively high in patients under rheumatologic follow-up. However, the use of biologics in these patients poses a low risk of HBVr. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA), the most prevalent autoimmune disease in reproductive years, exhibits a higher incidence in females, suggesting involvement of estrogens, genetics and environmental factors in disease onset. Literature shows smaller families in RA patients, driving increased interest in Assisted Reproductive Techniques. This review elucidates how immunotolerance mechanisms contribute to favorable pregnancy outcomes in RA, emphasizing the need for a careful pregnancy planning to mitigate fetal complications and postnatal flares, which surpass those in the general population. A thorough medication evaluation, orchestrated by a multidisciplinary team, is imperative during pregnancy, weighing potential teratogenic effects against safer alternatives to balance medication safety with disease control. A systematic literature search on PubMed and MEDLINE, using specific terms, covered relevant academic journals up to the latest date. This narrative review comprehensively addresses pregnancy-related considerations in RA patients, prioritizing meticulous disease management with pregnancy and breastfeeding-compatible drugs in line with the latest recommendations and registry data. The focus remains on evaluating glucocorticoids, conventional, and biological disease-modifying drugs for compatibility during pregnancy and breastfeeding. Additionally, the evolving landscape of targeted synthetic drugs during pregnancy is explored, providing insights into the latest developments in rheumatological care. [ABSTRACT FROM AUTHOR]

Objective: There are inconsistent reports regarding the relationship between cannabis use and male sexual function with almost no data about synthetic cannabinoids (SC) and their effect on male sexual functions. This study investigated psychological concerns related to male sexual functions among cannabis and SC users. The research assessed different sexual functions and aspects of sexual psychopathology in cannabis and SCs dependent men compared to controls. Method: Thirty male patients with cannabis dependence, thirty male patients with SCs dependence, and thirty matched controls from the outpatient clinic at Kasr Al Ainy hospital, Egypt, were assessed using the Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID-I), International Index of Erectile Function (IIEF), and Sexuality scale. Results: The means of IIEF questionnaire in the cannabis and SC group were significant lower (worse) than the means of the control group (P <.001) except the orgasmic function in cannabis group (P =.052). In the SCs group, sexual depression was higher and preoccupation lower than in the cannabis group (P <.020; P <.003, respectively) and control groups (P <.001; P <.001, respectively). The duration and dose of cannabis and SCs correlated significantly with sexual esteem, sexual preoccupation and all domains of IIEF. Conclusion: Cannabis and SC dependence were associated with lower erectile function, sexual desire, intercourse satisfaction and overall satisfaction, and lower orgasmic functions in the SC group than controls. Both groups showed higher sexual depression, lower sexual esteem and sexual preoccupation than controls. SC has a higher negative impact on male sexual functions and psychopathology than does cannabis. [ABSTRACT FROM AUTHOR]

Background: The simplest form of carbohydrate that the human body can utilize efficiently to fuel various functions in our body is glucose. The food that is consumed by us in any form is acted upon by pancreatic juices, bile, and several other digestive enzymes and is converted into its simplest form, which is absorbed by the small intestine and is diffused into the circulatory system; from there, it is transported to other organs via GLUT-2 and GLUT-4 transporters. This process is very important, and so are the hormones involved in it. One such major hormone responsible for glucose homeostasis in the body is insulin. Its malfunction or that of either of its signaling components leads to a metabolic disorder termed "diabetes." Hyperglycemia is a grave condition associated with this complex disease and is of global concern. The impact of this disease can be life threatening if adequate precaution, medication, and therapy are overlooked. A plethora of synthetic drugs are available in the market, and the main goals of these antidiabetic medicines are to improve insulin sensitivity and/or production as well as to lower blood glucose levels. In all cases, frequent use of antidiabetic medication causes several after-effects. Results: Numerous studies in this field demonstrate that antidiabetic phytomolecules are highly effective against diabetes patients and are almost completely without side effects. Almost all classes of phytomolecules have been thoroughly evaluated to develop the noble plant-based drug. Conclusion: The current review discusses diabetes, its classification and management, worldwide occurrence, and the most crucial class of antidiabetic phytomolecules, for example, alkaloids, and terpenenoids as well as the parent molecule responsible for the bioactivity, subclasses, their mechanisms of action, plant sources and part, their superiority over synthetic drug, and new advances in this area. [ABSTRACT FROM AUTHOR]

Although the current data are scarce and fragmentary, the misuse of electronic cigarette devices (ENDSs) for smoking illicit drugs poses a serious emergent threat to public health. This review emphasises the use of ENDSs as new tools for smoking illicit drugs. A comprehensive search using the terms "illicit drugs", "vape", and "electronic cigarettes" was conducted in PubMed, web-based drug forums, chat sites and grey literature combined with theterms tobacco, nicotine, smoking, cigarettes, cannabis, marijuana, opiate, opioid, heroin, cocaine, synthetic opioids/cannabinoids, cathinones, LSD, dimethyltryptamine (DMT), 3,4 methylenedioxymethamphetamine (MDMA), methamphetamine (Meth), vape/vaping, e-liquid and addiction. Studies were included if they met the following criteria: 1) involved human participants (Female, male, intersex); 2) consumed any type of illicit drug using electronic cigarette; 3) all ages were taken into consideration. We used all combinations of search terms from each category for articles published between January 2013 and October 2023 a long period due to the fact that in the last years ENDS cigarettes have undergone improvements in their structure having the ability to regulate the evaporation temperature and facilitate the potential for use of these devices to 'vape' illicit drugs. In addition to nicotine, the main vaped drugs were cannabis, cocaine and new psychoactive substances (NPSs), which included synthetic cannabinoids, synthetic opioids, hallucinogens and stimulant drugs. An increase in the risk of overdose and death with the use of NPSs is reported. Further work is urgently needed for a better understanding on the effect of vaping illicit drugs in the population. It is confirmed that ENDSs are becoming popular devices among both young and older individuals, with a mean age of use of 46.26 ± 16.8 years, as a new way of taking illicit drugs. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionThe widespread proliferation of high-potency synthetic opioids, particularly fentanyl, has precipitated a severe public health crisis in North America, with escalating overdose fatalities. Emerging concerns are observed in Australia, where recent incidents underscore the global impact of these substances. This study aimed to explore the role of synthetic opioids in overdoses among people in Queensland, Australia, and identify appropriate harm reduction responses from their perspective.Semi-structured interviews with 27 people who used opioids and who had experienced overdose in their lifetime were conducted. An iterative coding process, incorporating deductive and inductive codes, was employed.Participants emphasised the unpredictability and toxicity of the drug supply, especially with the presence of fentanyl. They highlighted the heightened risks due to decreased tolerance if there were periods of abstinence, and the challenges of using drugs in unsafe environments. There was strong support for safe consumption rooms to mitigate overdose risks.There are risks faced by people who use opioids due to an unpredictable and toxic drug supply, particularly with the presence of fentanyl. These findings underscore the importance of implementing proactive harm reduction strategies, including safe consumption spaces, to address the harms of synthetic opioids. [ABSTRACT FROM AUTHOR]

Worldwide, synthetic compounds are used for both in-office and at-home dental care. They are a valuable resource for both prophylactic and curative treatments for various dental problems, such as tooth decay, periodontal diseases, and many more. They are typically preferred due to their broad range of actions and ability to produce targeted, rapid, and long-lasting effects. Using a 0.12% chlorhexidine mouthwash is capable of reducing the plaque index from 47.69% to 2.37% and the bleeding index from 32.93% to 6.28% after just 2 weeks. Mouthwash with 0.1% OCT is also highly effective, as it significantly lowered the median plaque index and salivary bacterial counts in 152 patients in 5 days compared to a control group (p < 0.0001), while also reducing the gingival index (p < 0.001). When povidone-iodine was used as an irrigant during the surgical removal of mandibular third molars in 105 patients, it resulted in notably lower pain scores after 2 days compared to a control group (4.57 ± 0.60 vs. 5.71 ± 0.45). Sodium hypochlorite is excellent for root canal disinfection, as irrigating with 1% NaOCl completely eliminated the bacteria from canals in 65% patients. A 0.05% CPC mouthwash proved effective for perioperative patient care, significantly decreasing gingival bleeding (p < 0.001) and suppressing Streptococcus levels even one week post-surgery. Lastly, a 6% H2O2 paint-on varnish and 6% H2O2 tray formulations successfully bleached the teeth of 40 patients, maintaining a noticeably whiter appearance up to the 6-month follow-up, with significant color differences from the baseline (p < 0.005). Synthetic compounds have a large research base, which also provides a greater awareness of their mechanism of action and potential adverse effects. For a better understanding of how they work, several methods and assays are performed. These are protocolary techniques through which a compound's efficacy and toxicity are established. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite recent advances in treatment options, such as chemotherapy, cancer continues to be the second-leading cause of death worldwide. Significant hurdles in the success of chemotherapy regimens include severe adverse effects, as well as drug resistance. As such, there is a strong requirement for novel pharmacological interventions in the treatment of cancer. Natural products, such as monosaccharides, are a promising potential treatment option for cancer due to their low toxicity, high solubility, and high specificity for tumour cells. Several naturally occurring and synthetically modified sugars have displayed toxicity in a variety of cancer and tumour cells. A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake and consumption of glucose. The Warburg effect may be exploited in the treatment of cancer; certain epimers and derivatives of glucose can enter cancer cells and inhibit glycolytic enzymes, stunting metabolism and causing cell death. These include common dietary monosaccharides (ᴅ-mannose, ᴅ-galactose, ᴅ-glucosamine, ʟ-fucose), as well as some rare monosaccharides (xylitol, ᴅ-allose, ʟ-sorbose, ʟ-rhamnose). This article reviews the literature on these sugars in in vitro and in vivo models of cancer, discussing their mechanisms of cytotoxicity. In addition to this, the anticancer potential of some synthetically modified monosaccharides, such as 2-deoxy-ᴅ-glucose and its acetylated and halogenated derivatives, is reviewed. Further, this article reviews how certain monosaccharides can be used in combination with anticancer drugs to potentiate conventional chemotherapies and to help overcome chemoresistance. Finally, the limitations of administering two separate agents, a sugar and a chemotherapeutic drug, are discussed. The potential of the glycoconjugation of classical or repurposed chemotherapy drugs as a solution to these limitations is reviewed. [ABSTRACT FROM AUTHOR]

The natural ingredient-based therapy extracted from various plants is assumed more tolerable to cancer patients' bodies than synthetic drugs. To tell successful novel cancer therapy, an indicator is needed to confirm the result. VEGF is a pro-angiogenic factor that leads the cancer cells' invasion to another organ and is associated with high mortality in patients. Hence, the VEGF level is widely used as one of the successful cancer therapy indicators. Purposed of research elucidated the effect of Mandarin orange peel ethanol extract (EEKJM) to improve the reduction of VEGF levels in colon cancer in vitro. This study was an experimental posttest and control group design to analyze different level of VEGF on cancer cells at end of the study. Research began with the preparation of EEKJM followed by a cytotoxic extract test using the MTT assay method. Furthermore, the measurement of VEGF levels by the VEGF ELISA kit protocol. One Way ANOVA was performed to analyze data. Results showed the cytotoxic test of the EEKJM and doxorubicin against WiDr cells was 240 g/ml and 1.59 µg/ml. VEGF levels showed decreasing after being induced with EEKJM and doxorubicin with doses ½ IC50 and ¼ IC50. Conclusion: EEKJM was able to reduce VEGF levels and viability of WiDr colon cancer cells. The advantages are as much as initial evidence of the ability of the orange to treat cancer even though further animal studies or evidence of a pathway of decrease of the VEGF or other signals are required. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy. [ABSTRACT FROM AUTHOR]

Background: The recreational use of LSD, a synthetic psychedelic drug, has surged in recent years, coinciding with a renewed research focus on its potential psychotherapeutic properties. Aim: This study aims to describe the experiences and perceptions of individuals engaging in LSD use for the first time, derived from a large international sample. Methods: This study utilised 2018 Global Drug Survey data collected from 6 November 2017 to 10 January 2018. Participants who initiated LSD use in the preceding 12 months answered questions on their experiences, social settings, harm-reduction behaviours, and demographics. Descriptive statistics were employed, and characteristics of those seeking emergency medical treatment (EMT) and those not planning further LSD use were compared with other respondents. Results: Among 3340 respondents who used LSD in the past year, their first-time experiences generally exceeded expectations, with 97.7% expressing excitement. Adverse and unwanted side effects were rarely reported, and only 17 individuals needed EMT. Feelings of fear were reported by most (64.1%), but only very mildly and not enough to put them off from wanting to use LSD again. Discussion: Although the occurrence of unwanted side effects seems low and the LSD experience is generally pleasurable, vigilance amid the rising illicit use of LSD through harm-reduction education is still important in preventing possible risks. [ABSTRACT FROM AUTHOR]

Objectives To investigate if disease activity among elderly RA patients >75 years of age has changed over time in the real-world clinical setting. Methods Data from an observational multicentre registry of RA patients in Japan were analysed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (>75 years) who achieved remission and low disease activity (LDA), from 2014 to 2021. The secondary outcome was to identify factors associated with remission and LDA by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression. Results A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients >75 years of age increased from 16.5% to 26.9%, with biologics and targeted synthetic DMARDs (b/tsDMARDs) use increasing and glucocorticoids use decreasing, while conventional synthetic DMARDs use remained relatively stable. The proportion of RA patients >75 years of age achieving remission and LDA significantly increased from 62.2% to 78.2% (P for trend < 0.001). A negative factor associated with achieving remission and LDA was glucocorticoid use, seropositivity and a history of previous b/tsDMARDs use while MTX use was associated positively, independent of other predictors. Conclusions In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Cancer research is an on-going field aimed at discovering novel treatments for various stages of the disease. Although chemo and hormonal therapy have been found to be effective in treating cancer, there are still challenges draw a parallel with them, such as therapeutic resistance and repetitiveness, which make the disease difficult to control. Therefore, it is imperative to explore alternative therapies that can provide better treatment outcomes. The present research work towards the potential use of phytochemicals, particularly flavonoids found in Citrus medica leaves, as a treatment for breast cancer. Using chromatographic techniques, flavanone, a compound found in citrus extract, was isolated and its structure was characterized using UV, FTIR, HPLC, NMR, and MS analyses, as well as comparisons with literature. The anticancer activity of flavanone was evaluated using a standard MTT test against commonly used breast cancer cell(MCF-7). Additionally, the present study investigated the combination effect of flavanone with a synthetic drug, 2-deoxy-D-glucose (2DG), on MCF-7 cells. The findings reveal that flavanone and the combined flavones with 2DG had IC50 values of 57.10 and 34.09 μg/mL, respectively. This fusion study provides promising evidence that the combined effect of flavanone with a synthetic drug may enhance treatment effectiveness by improving drug transport and reducing the required dose. Additional study is required to confirm these results and investigate phytochemicals' potential as a replacement therapy for breast cancer. [ABSTRACT FROM AUTHOR]

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stemcells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and nongenetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions. [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to assess the accuracy of expert predictions, which were derived using a Delphi panel foresight study between 2009 and 2011, on a variety of drug-related topics in Finland in 2020. Methods: The material used to evaluate the accuracy of the predictions consists of published reports on statistics, survey results, official register data, wastewater analyses and official documents. Whenever possible, we used multiple information sources to ascertain possible changes related to the predictions. Results: Between 2009 and 2011, the majority – but not all – of the experts accurately predicted an increase in drug use. Indeed, more people experimented with or used drugs, and more drug residues were found in wastewater monitoring. The experts also correctly predicted an increase in population-level approval of drug use, but this development has been rather slow. Contrary to predictions, there was no marked increase in the use of new synthetic drugs. However, the misuse of buprenorphine increased during the 2010s. In the drug market, unit prices were surprisingly stable over the ten-year period. There were no changes in legislation related to the legal status of drugs, as was foreseen by the experts. However, enforcement moved in the direction foreseen by the experts: more lenient measures have been taken against users. Drug care system reforms favored a combination of mental health and addiction care units between 2009 and 2011, and 2020, as foreseen by the experts. Conclusions: It seems to have been easier for the experts to foresee the continuation of existing trends, e.g., increasing use of drugs or widening approval of drugs, than to predict possible changes in the popularity of distinct groups of drugs such as new psychoactive substances (NPS). Even armed with the prediction that drug imports and wholesale would increasingly fall into the domain of organized crime, this undesirable development could not be stopped. Expert disagreement can also be seen as a valuable indication of uncertainty regarding the future. Foresight related to drug-related issues can produce relatively accurate and realistic views of the future at least up to ten years ahead. [ABSTRACT FROM AUTHOR]

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, this study aimed to demonstrate, for the first time, the antibacterial activity of phytocompound ASTA against S. mutans. The findings revealed that ASTA significantly inhibited the growth of S. mutans and the production of virulence factors such as acidurity, acidogenicity, and eDNA synthesis. Molecular docking analysis evaluated the potential activity of ASTA against S. mutans virulence genes, including VicR and GtfC. Furthermore, toxicity assessment of ASTA in human buccal epithelial cells was performed, and no morphological changes were observed. An in vivo analysis using Danio rerio (zebrafish) confirmed that the ASTA treatment significantly increased the survival rates of infected fish by hindering the intestinal colonization of S. mutans. Furthermore, the disease protection potential of ASTA against the pathognomonic symptom of S. mutans infection was proven by the histopathological examination of the gills, gut, and kidney. Overall, these findings suggest that ASTAmay be a promising therapeutic and alternative drug for the treatment and prevention of oral infection imposed by S. mutans. [ABSTRACT FROM AUTHOR]

In modern medicine, synthetic drugs are predominant, yet they often pose health hazards. So, there is a need to find natural alternatives. Ziziphus nummularia (Burm. F.) Wight & Arn., belongs to family Rhamnaceae, is well known for its traditional value such as its fruits have been used as natural appetizer and orally consumed around the world. This study investigated the phytochemical composition and bioactivity of crude and fractionated extracts from the stem bark of Ziziphus nummularia. Crude extracts were prepared using cold maceration, followed by partitioning based on polarity into n-hexane, chloroform, and ethyl acetate fractions. These extracts were subjected to phytochemical analysis and evaluated for antioxidant, antibacterial, and cytotoxic activities. The crude methanolic extract exhibited the highest antioxidant activity, with IC50 values of 136.49 μg/mL in DPPH and 78.9 μg/mL in ABTS assays. Antibacterial tests using the agar well diffusion method revealed that the methanolic extract, ethyl acetate, and chloroform fractions demonstrated broad-spectrum antibacterial activity against E. coli, K. pneumoniae, S. aureus, and S. epidermidis, with inhibition zones ranging from 0 to 8.43 ± 0.23 mm at 400 mg/mL. The brine shrimp lethality assay indicated significant cytotoxicity in the methanolic, ethyl acetate, and chloroform extracts, compared to the negligible effect of the n-hexane fraction. These findings highlight the potential of Z. nummularia as a source of bioactive compounds with therapeutic applications against infectious diseases, toxins, and oxidative stress. Further isolation of pure compounds and animal trials are recommended to explore its potential in drug discovery. [ABSTRACT FROM AUTHOR]

Inflammation, a widespread biological process linked to various diseases, poses a significant global health challenge. Recent research targeting the development of new anti-inflammatory drugs has prioritized plant-derived compounds due to their cost-effectiveness and minimal side effects compared to synthetic drugs. Flavonoids, polyphenolic compounds in plants, show potential for treating inflammation-related diseases. This study evaluates the anti-inflammatory activity of flavonoids from the Knema genus, a member of the Myristicaceae family. We focused on inhibiting two pro-inflammatory proteins, human and murine interleukin-1B (IL-1) and human interleukin-6 (IL-6). Molecular docking and ADMET prediction identified sulfuretin and (-)-catechin with high binding affinity to IL-6, whereas 4'-hydroxy-7-methoxyflavanone and 7,2'-dihydroxy-6,8-dimethyl-4',5'-methylenedioxyflavan stably bind IL-6. Molecular interaction analyses revealed that hydrogen and π--σ bonds contribute to the interaction. Notably, these flavonoids exhibited affinities comparable to celecoxib. Our computational predictions support the suitability of these flavonoids as drug candidates, indicating their promise as natural anti-inflammatory agents capable of modulating pro-inflammatory signaling pathways. [ABSTRACT FROM AUTHOR]

Polyphenols are natural bioactives occurring in medicinal and aromatic plants and food and beverages of plant origin. Compared with conventional therapies, plant-derived phytochemicals are more affordable and accessible and have no toxic side effects. Thus, pharmaceutical research is increasingly inclined to discover and study new and innovative natural molecules for the treatment of several chronic human diseases, like type 2 diabetes mellitus (T2DM) and osteoporosis. These pathological conditions are characterized by a chronic inflammatory state and persistent oxidative stress, which are interconnected and lead to the development and worsening of these two health disorders. Oral nano delivery strategies have been used to improve the bioavailability of polyphenols and to allow these natural molecules to exert their antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic biological activities in in vivo experimental models and in patients. Polyphenols are commonly used in the formulations of nutraceuticals, which can counteract the detrimental effects of T2DM and osteoporosis pathologies. This review describes the polyphenols that can exert protective effects against T2DM and osteoporosis through the modulation of specific molecular markers and pathways. These bioactives could be used as adjuvants, in combination with synthetic drugs, in the future to develop innovative therapeutic strategies for the treatment of T2DM and osteoporosis. [ABSTRACT FROM AUTHOR]

Consumers generally prefer natural to synthetic drugs, a phenomenon known as the "natural preference." Through six experiments and one archival study, the current research shows that while consumers have a general preference for natural drugs over synthetic drugs, this preference is stronger when the goal is to treat psychological rather than physical conditions. Process evidence indicates an important mechanism that explains the amplified natural preference for treating psychological conditions: Consumers are more concerned about their true selves being altered when treating psychological conditions, and they perceive natural drugs to be less likely than synthetic drugs to affect their true selves. The current research provides novel insights into the natural preference. It also offers policy and managerial implications for marketing natural remedies and pharmacological treatments for mental health conditions. [ABSTRACT FROM AUTHOR]

The potential for synthetic cannabinoids (SCs) to function as an alternative to marijuana without the same risk of a positive urinalyses led to claims of pervasive military SC use. Case studies confirm use among veterans, but no study has adequately explored SC use in the military using detailed interview data. Interviews (1-2 h) were conducted with 318 justice-involved veterans. Recruitment was attempted with all participants in eight veterans treatment courts in three U.S. states (54.9% of 579 eligible veterans). Interviews were transcribed and thematic analyses completed. SC use was reported by 65 participants (21.3%). Major emergent themes indicated SCs were perceived as unpleasant, overly powerful, and a poor substitute for marijuana. Further, habitual use was rare as many chose not to reuse after initial negative experiences. Few indicated that the perception that SCs would not appear on routine military urinalyses enabled their use. Veterans were aware of the changing drug composition and feared "bad batches." SCs were explicitly disliked both independently and relative to marijuana. Nine discussed avoiding positive military drug screens as a consideration, but negative initial experiences generally prevented progression to habitual use. Veterans did not view SCs as a suitable marijuana replacement. Fears that SCs are being used as a marijuana alternative among veterans subject to frequent drug testing appear unfounded. These interviews suggest that routine military drug testing did not motivate individuals to use SCs habitually as a marijuana replacement; however, veterans' negative interpretation of SC effects contributed to this outcome. [ABSTRACT FROM AUTHOR]

Polysaccharides are a kind of biological macromolecule, which widely exists in plants, fungi, animals, microorganisms, and other organisms. Polysaccharides exhibit various biological activities such as immunological regulation, antioxidation, antitumor, antiinflammatory, regulating intestinal flora, and protecting liver. These biological activities depend on their structure and physicochemical properties including monosaccharide composition, molecular weight (Mw), spatial configuration, etc. However, biological activities of polysaccharides are hardly comparable to synthetic drugs due to their inherent physicochemical properties. Therefore, structural modification of polysaccharides is an effective way to enhance their biological activities and promote the presentation of bioactivity. At present, phosphorylation modification is a common chemical modification method, which can effectively improve the biological activities of polysaccharides. However, there are limited reports on the synthesis, structure identification, and biological activities of phosphorylated polysaccharides. In view of this, the synthesis methods, structure identification methods, and biological activities of phosphorylated polysaccharides are reviewed in this paper. The findings can provide useful guidance for the research, production, and application of phosphorylated polysaccharides in functional foods and therapeutic agents. [ABSTRACT FROM AUTHOR]

The objective of this meta‐epidemiological study was to explore the impact of attrition rates on treatment effect estimates in randomised trials of chronic inflammatory diseases (CID) treated with biological and targeted synthetic disease‐modifying drugs. We sampled trials from Cochrane reviews. Attrition rates and primary endpoint results were retrieved from trial publications; Odds ratios (ORs) were calculated from the odds of withdrawing in the experimental intervention compared to the control comparison groups (i.e., differential attrition), as well as the odds of achieving a clinical response (i.e., the trial outcome). Trials were combined using random effects restricted maximum likelihood meta‐regression models and associations between estimates of treatment effects and attrition rates were analysed. From 37 meta‐analyses, 179 trials were included, and 163 were analysed (301 randomised comparisons; n = 62,220 patients). Overall, the odds of withdrawal were lower in the experimental compared to control groups (random effects summary OR = 0.45, 95% CI, 0.41–0.50). The corresponding overall treatment effects were large (random effects summary OR = 4.43, 95% CI 3.92–4.99) with considerable heterogeneity across interventions and clinical specialties (I2 = 85.7%). The ORs estimating treatment effect showed larger treatment benefits when the differential attrition was more prominent with more attrition in the control group (OR = 0.73, 95% CI 0.55–0.96). Higher attrition rates from the control arm are associated with larger estimated benefits of treatments with biological or targeted synthetic disease‐modifying drugs in CID trials; differential attrition may affect estimates of treatment benefit in randomised trials. [ABSTRACT FROM AUTHOR]

Plant derivatives are gaining significant momentum in the field of medical science due to their broadspectrum therapeutic properties owing to drug resistance and harmful side effects associated with synthetic drugs. Staphylococcus aureus, is known for its multidrug-resistance against common antibiotics and is responsible for spreading various pathogenic diseases. The present in vitro investigation aimed to assess the antibacterial potential of methanolic extracts of Mikania micrantha, Corchorus capsularis and Centella asiatica plant against the gram-positive bacteria S. aureus (MTCC 7443) strain. Employing the agar well diffusion method, antibacterial activity at various concentrations of the plant extracts were evaluated. The results demonstrated a significant zone of inhibition (p=0.05) for all the selected plant extracts. The plant extract from Mikania micrantha exhibited an inhibition zone of 14.7±0.71 mm and 19.33±0.58 mm; Corchorus capsularis showed 9.44±0.69 mm and 12.11±0.38 mm, while Centella asiatica showed 11.33±0.96 mm and 13.22±0.38 mm at 80 mg and 120 mg concentrations, respectively. The positive control demonstrated an inhibition zone of 11.23 mm whereas, the negative control showed no zone of inhibition. These findings suggest that the plant extracts possess a broad-spectrum antibacterial activity against the pathogenic bacterial strain, indicating their potential as a source of natural antibacterial compounds. [ABSTRACT FROM AUTHOR]

Objective: We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease‐modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice. Methods: Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression. Results: In the year before drug starts, 65.6% of patients had any TB screening; in a 3‐year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin‐17 inhibitors (IL‐17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year. Conclusion: We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL‐17i and among Asian and Hispanic patients, as well as low‐performing practices. Educational initiatives, team‐based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed. [ABSTRACT FROM AUTHOR]