Clinical applications and mechanism insights of natural flavonoids against type 2 diabetes mellitus.

Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.

Influence of Maqian essential oil on gut microbiota and immunoresponses in type 1 diabetes: In silico study.

Diversity and homeostasis of gut bacterial composition is highly associated with the pathogenesis of insulin dysfunction and type 1 diabetes melittus (T1D), hence emerged in parallel with the activation of autoimmunity. We aimed to study the bioactive potential of essential oil from Zanthoxylum myriacanthum var. pubescens Huang (Maqian) through computational approaches. Twelve chemical constituents derived from Maqian essential oil were docked with selected proteins (i.e., 3pig, 1kho, 7dmq, 4m4d, 2z65, 4glp, and 3fxi) in which are involved in gut microbiota modulation in T1D. Subsequently, the prediction of bioavailability properties of the small molecules were evaluated. Among all chemical constituents, the post-docking interaction analysis demonstrated that α-phellandrene exhibits the strongest binding affinity and induces gut microbiota modulation with ß-fructofuranosidase from Bifidobacterium longum. The current result revealed the potential of 3-Carene and α-Pinene in inducing specific changes in gut microbiota downregulating Clostridium perfringens and quenching Leptotrichia shahii respectively. ß-Pinene possess exceptionally strong binding affinity that effectively disrupt the interaction between lipopolysaccharide and its cognate receptors, while α-Phellandrene was exhibited the uppermost binding affinity with TLR4/MD2 and could likely target TLR4 stimulating lipopolysaccharide. Our results are the first to report on the gut microbiota modulation effects of α-Phellandrene and ß-Phellandrene via actions on LPS binding to CD14 and the TLR4 co-receptor signaling. In conclusion, our findings based on computational approaches, small molecules from Maqian present as promising agents which could regulate inflammatory response and modulate gut microbiota in type 1 diabetes mellitus.

Design of three-component essential oil extract mixture from Cymbopogon flexuosus, Carum carvi, and Acorus calamus with enhanced antioxidant activity.

The development of novel antioxidant compounds with high efficacy and low toxicity is of utmost importance in the medicine and food industries. Moreover, with increasing concerns about the safety of synthetic components, scientists are beginning to search for natural sources of antioxidants, especially essential oils (EOs). The combination of EOs may produce a higher scavenging profile than a single oil due to better chemical diversity in the mixture. Therefore, this exploratory study aims to assess the antioxidant activity of three EOs extracted from Cymbopogon flexuosus, Carum carvi, and Acorus calamus in individual and combined forms using the augmented-simplex design methodology. The in vitro antioxidant assays were performed using DPPH and ABTS radical scavenging approaches. The results of the Chromatography Gas-Mass spectrometry (CG-MS) characterization showed that citral (29.62%) and niral (27.32%) are the main components for C. flexuosus, while D-carvone (62.09%) and D-limonene (29.58%) are the most dominant substances in C. carvi. By contrast, ß-asarone (69.11%) was identified as the principal component of A. calamus (30.2%). The individual EO exhibits variable scavenging activities against ABTS and DPPH radicals. These effects were enhanced through the mixture of the three EOs. The optimal antioxidant formulation consisted of 20% C. flexuosus, 53% C. carvi, and 27% A. calamus for DPPHIC50. Whereas 17% C. flexuosus, 43% C. carvi, and 40% A. calamus is the best combination leading to the highest scavenging activity against ABTS radical. These findings suggest a new research avenue for EOs combinations to be developed as novel natural formulations useful in food and biopharmaceutical products.

Effectiveness of digital tools for smoking cessation in Asian countries: a systematic review.

AIM: The use of tobacco is responsible for many preventable diseases and deaths worldwide. Digital interventions have greatly improved patient health and clinical care and have proven to be effective for quitting smoking in the general population due to their flexibility and potential for personalization. However, there is limited evidence on the effectiveness of digital interventions for smoking cessation in Asian countries. METHODS: Three major databases - Web of Science (WOS), Scopus, and PubMed - for relevant studies published between 1 January 2010 and 12 February 2023 were searched for studies evaluating the effectiveness of digital intervention for smoking cessation in Asian countries. RESULTS: A total of 25 studies of varying designs were eligible for this study collectively involving a total of n = 22,005 participants from 9 countries. Among different digital tools for smoking cessation, the highest abstinence rate (70%) was reported with cognitive behavioural theory (CBT)-based smoking cessation intervention via Facebook followed by smartphone app (60%), WhatsApp (59.9%), and Pharmacist counselling with Quit US smartphone app (58.4%). However, WhatsApp was preferred over Facebook intervention due to lower rates of relapse. WeChat was responsible for 15.6% and 41.8% 7-day point prevalence abstinence. For telephone/text messaging abstinence rate ranged from 8-44.3% and quit rates from 6.3% to 16.8%. Whereas, no significant impact of media/multimedia messages and web-based learning on smoking cessation was observed in this study. CONCLUSION: Based on the study findings the use of digital tools can be considered an alternative and cost-effective smoking cessation intervention as compared to traditional smoking cessation interventions.

The Use of ChatGPT for Education Modules on Integrated Pharmacotherapy of Infectious Disease: Educators' Perspectives.

BACKGROUND: Artificial Intelligence (AI) plays an important role in many fields, including medical education, practice, and research. Many medical educators started using ChatGPT at the end of 2022 for many purposes. OBJECTIVE: The aim of this study was to explore the potential uses, benefits, and risks of using ChatGPT in education modules on integrated pharmacotherapy of infectious disease. METHODS: A content analysis was conducted to investigate the applications of ChatGPT in education modules on integrated pharmacotherapy of infectious disease. Questions pertaining to curriculum development, syllabus design, lecture note preparation, and examination construction were posed during data collection. Three experienced professors rated the appropriateness and precision of the answers provided by ChatGPT. The consensus rating was considered. The professors also discussed the prospective applications, benefits, and risks of ChatGPT in this educational setting. RESULTS: ChatGPT demonstrated the ability to contribute to various aspects of curriculum design, with ratings ranging from 50% to 92% for appropriateness and accuracy. However, there were limitations and risks associated with its use, including incomplete syllabi, the absence of essential learning objectives, and the inability to design valid questionnaires and qualitative studies. It was suggested that educators use ChatGPT as a resource rather than relying primarily on its output. There are recommendations for effectively incorporating ChatGPT into the curriculum of the education modules on integrated pharmacotherapy of infectious disease. CONCLUSIONS: Medical and health sciences educators can use ChatGPT as a guide in many aspects related to the development of the curriculum of the education modules on integrated pharmacotherapy of infectious disease, syllabus design, lecture notes preparation, and examination preparation with caution.

2D nanostructures: Potential in diagnosis and treatment of Alzheimer's disease.

Two-dimensional (2D) nanomaterials have garnered enormous attention seemingly due to their unusual architecture and properties. Graphene and graphene oxide based 2D nanomaterials remained the most sought after for several years but the quest to design superior 2D nanomaterials which can find wider application gave rise to development of non-graphene 2D materials as well. Consequently, in addition to graphene based 2D nanomaterials, 2D nanostructures designed using macromolecules (such as DNAs, proteins, peptides and peptoids), transition metal dichalcogenides, transition-metal carbides and/or nitrides (MXene), black phosphorous, chitosan, hexagonal boron nitrides, and graphitic carbon nitride, and covalent organic frameworks have been developed. Interestingly, these 2D nanomaterials have found applications in diagnosis and treatment of various diseases including Alzheimer's disease (AD). Although AD is one of the most debilitating neurodegenerative conditions across the globe; unfortunately, there remains a paucity of effective diagnostic and/or therapeutic intervention for it till date. In this scenario, nanomaterial-based biosensors, or therapeutics especially 2D nanostructures are emerging to be promising in this regard. This review summarizes the diagnostic and therapeutic platforms developed for AD using 2D nanostructures. Collectively, it is worth mentioning that these 2D nanomaterials would seemingly provide an alternative and intriguing platform for biomedical interventions.

Tetraclinis articulata (Vahl) Mast. essential oil as a promising source of bioactive compounds with antimicrobial, antioxidant, anti-inflammatory and dermatoprotective properties: In vitro and in silico evidence.

Tetraclinis articulata is a known traditional medicinal plant used to manage various ailments, such as diabetes, rheumatism and infectious diseases. This study aims to determine the chemical constituents of T. articulata essential oil (EO) and to evaluate its in vitro antibacterial, anti-candidal, antioxidant, anti-inflammatory and dermatoprotective properties. In addition, a computational docking approach was used to predict the potential antioxidant, antibacterial, antifungal, anti-inflammatory, and cytotoxic properties of the identified compounds. The volatile oil obtained by hydrodistillation was characterized using gas chromatography-mass spectrometry (GC-MS). The antioxidant activity of T. articulata EO was investigated using three complementary assays: DPPH, ABTS and FRAP. Lipoxygenase (5-LOX) and tyrosinase enzymes were used to assess the anti-inflammatory and dermatoprotective effects of this oil. Moreover, disc-diffusion technique, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays were employed for the antimicrobial screening. The GC-MS analysis revealed that bornyl acetate (41.80 %), α-pinene (17.97 %) and camphor (15.97 %) are the major components of the studied EO. Moreover, T. articulata EO has exhibited promising antioxidant effect on FRAP, DPPH, and ABTS experiments. It also significantly inhibited 5-LOX (IC50 = 67.82 ± 0.03 µg/mL) and tyrosinase (IC50 = 211.93 ± 0.02 µg/mL). The results of MIC and MBC assays indicated that T. articulata EO is able to inhibit the growth of all tested bacteria (Gram + and Gram -) and Candida species. The ratio of tolerance level indicated that the tested oil was bactericidal against the Gram + bacteria and Candida species, whereas it has a bacteriostatic behavior against the Gram- bacteria. In light of these findings, T. articulata EO may be suggested as a potential pharmaceutical agent to prevent inflammation and skin problems and may serve as a natural antimicrobial and antioxidant alternative for sustainable application in food products.

Saussurea costus (Falc.) Lipsch.: a comprehensive review of its pharmacology, phytochemicals, ethnobotanical uses, and therapeutic potential.

Saussurea costus (Falc.) Lipsch., commonly known as costus, is a perennial herb that has been traditionally used in various indigenous medicinal systems across Asia. Its historical prominence in traditional remedies underscores the need to explore its phytochemical composition, pharmacological properties, and potential therapeutic benefits. This review aims to provide a comprehensive overview of the available literature on the pharmacological properties, phytochemical constituents, ethnobotanical uses, and therapeutic potential of S. costus. An exhaustive search was performed across multiple electronic databases, including PubMed/MedLine, Google Scholar, Web of Science, Scopus, TRIP database, and Science Direct. Both experimental and clinical studies, as well as traditional ethnobotanical records, were considered for inclusion. The phytochemical analysis revealed that S. costus contains a plethora of bioactive compounds, including sesquiterpenes, flavonoids, and essential oils, which are responsible for its myriad of medicinal properties. The pharmacological studies have demonstrated its anti-inflammatory, anti-oxidant, anti-cancer, hepatoprotective, and immunomodulatory effects, among others. Ethnobotanical data showcased its extensive use in treating ailments like asthma, digestive disorders, and skin conditions. Some clinical trials also underscore its efficacy in certain health conditions, corroborating its traditional uses. S. costus possesses significant therapeutic potential, largely attributable to its rich phytochemical composition; the convergence of its traditional uses and modern pharmacological findings suggests promising avenues for future research, especially in drug development and understanding its mechanism of action in various ailments.

Bioactive substances of cyanobacteria and microalgae: Sources, metabolism, and anticancer mechanism insights.

Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.

Proximate composition, lipid and elemental profiling of eight varieties of avocado (Persea americana).

Eight Moroccan avocado varieties were analyzed for their nutritional composition and physicochemical properties. The nutritional contents of the sample were determined through the evaluation of the moisture, oil, ash, protein, and carbohydrate contents, and energy value calculation. Additionally, macroelements (Ca, Mg, and Na) and microelements (Fe, Zn, Cu, and Mn) were determined in the mineral profile. Oils were examined also for their fatty acid, phytosterol, and tocopherol profiles. As a result of the study, the avocado presents significant differences between the eight studied varieties (p < 0.05), with regard to moisture content (57.88 g/100 g to 84.71 g/100 g), oil content (8.41 g/100 g to 57.88 g/100 g), ash (0.57 g/100 g to 1.37 g/100 g), protein content (5.7 g/100 g to 8.61 g/100 g), carbohydrate content (5.63 g/100 g to 14.61 g/100 g), and energy value (99.9 kcal/100 g to 316.8 kcal/100 g). Sodium (5783.01 mg/kg to 12,056.19 mg/kg) was the predominant macro-element in all varieties, followed by calcium (295.95 mg/kg to 531.67 mg/kg), and magnesium (246.29 mg/kg to 339.84 mg/kg). Copper (85.92 mg/kg to 112. 31 mg/kg) was the main microelement in all varieties, followed by iron (8.5 mg/kg to 20.32 mg/kg), and manganese (7.3 mg/kg to 18.45 mg/kg), while zinc (1.72 mg/kg to 5.66 mg/kg) was detected in small amounts. In addition, significant difference was observed in lipid profiles, according to the eight studied varieties (p < 0.05). Avocado oils were mainly composed of monounsaturated fatty acids (76.89 g/100 g to 84.7 g/100 g), with oleic acid (50.38 g/100 g to 71.49 g/100 g) standing out as particularly characteristic, while ß-sitosterol (l2365.58 mg/kg to 4559.27 mg/kg), and α-tocopherol (30.08 mg/kg to 182.94 mg/kg) were among its major phytosterols and tocopherols. All avocado varieties represented in this study can be consumed as a fruit as an excellent source of energy, minerals, fatty acids, phytosterols, and tocopherols. The regular consumption of this fruit provides the body with several essential nutrients.

Phytosterols activating nuclear receptors are involving in steroid hormone-dependent cancers: Myth or fact?

Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.

Assessing the Protective Role of Epigallocatechin Gallate (EGCG) against Water-Pipe Smoke-Induced Toxicity: A Comparative Study on Gene Expression and Histopathology.

Exposure to water-pipe smoking, whether flavored or unflavored, has been shown to instigate inflammation and oxidative stress in BALB/c mice. This consequently results in alterations in the expression of inflammatory markers and antioxidant genes. This study aimed to scrutinize the impact of Epigallocatechin gallate (EGCG)-a key active component of green tea-on inflammation and oxidative stress in BALB/c mice exposed to water-pipe smoke. The experimental setup included a control group, a flavored water-pipe smoke (FWP) group, an unflavored water-pipe smoke (UFWP) group, and EGCG-treated flavored and unflavored groups (FWP + EGCG and UFWP + EGCG). Expression levels of IL-6, IL1B, TNF-α, CAT, GPXI, MT-I, MT-II, SOD-I, SOD-II, and SOD-III were evaluated in lung, liver, and kidney tissues. Histopathological changes were also assessed. The findings revealed that the EGCG-treated groups manifested a significant decline in the expression of inflammatory markers and antioxidant genes compared to the FWP and UFWP groups. This insinuates that EGCG holds the capacity to alleviate the damaging effects of water-pipe smoke-induced inflammation and oxidative stress. Moreover, enhancements in histopathological features were observed in the EGCG-treated groups, signifying a protective effect against tissue damage induced by water-pipe smoking. These results underscore the potential of EGCG as a protective agent against the adverse effects of water-pipe smoking. By curbing inflammation and oxidative stress, EGCG may aid in the prevention or mitigation of smoking-associated diseases.

Combination of sweet orange, lentisk and lemon eucalyptus essential oils: Optimization of a new complete antimicrobial formulation using a mixture design methodology.

Sweet orange (Citrus × sinensis (L.) Osbeck), lentisk (Pistacia lentiscus L.) and lemon eucalyptus (Eucalyptus citriodora Hook) are medicinal plants known by its culinary virtues. Their volatile oils have demonstrated promising antimicrobial activity against a panel of microbial strains, including those implicated in food deterioration. In this exploratory investigation, we aimed to determine the antimicrobial formulation of sweet orange, lentisk and lemon eucalyptus essential oils (EOs) using the simplex-centroid mixture design approach coupled with a broth microdilution method. EOs were first extracted by hydrodistillation, and then their phytochemical profile was characterized using Gas chromatography-mass spectrometry (GC-MS). GC-MS analysis identified d-limonene (14.27%), careen-3 (14.11%), ß-myrcene (12.53%) as main components of lentisk EOs, while lemon eucalyptus was dominated by citronellal (39.40%), ß-citronellol (16.39%) and 1,8-cineole (9.22%). For sweet orange EOs, d-limonene (87.22%) was the principal compound. The three EOs exhibited promising antimicrobial potential against various microorganisms. Lemon eucalyptus and sweet orange EO showed high activity against most tested microorganisms, while lentisk EO exerted important effect against some microbes but only moderate activity against others. The optimization formulations of antimicrobial potential showed interesting synergistic effects between three EOs. The best combinations predicted on C. albicans, S. aureus, E. coli, S. enterica and B. cereus correspond to 44%/55%/0%, 54%/16%/28%, 43%/22%/33%, 45%/17%/36% and 36%/30%/32% of Citrus sinensis, Pistacia lentiscus and Eucalyptus citriodora EOs, respectively. These findings suggest that the combination of EOs could be used as natural food preservatives and antimicrobial agents. However, further studies are needed to determine the mechanisms of action and efficacy of these EOs against different microorganisms.

Expediting Multiple Biological Properties of Limonene and α-Pinene: Main Bioactive Compounds of Pistacia lentiscus L., Essential Oils.

BACKGROUND: Screening new natural molecules with pharmacological and/or cosmetic properties remains a highly sought-after area of research. Moreover, essential oils and volatile compounds have recently garnered significant interest as natural substance candidates. In this study, the volatile components of Pistacia lentiscus L. essential oils (PLEOs) isolated from the fruit and its main compounds, alpha-pinene, and limonene, are investigated for antioxidant, antidiabetic, and dermatoprotective activities. METHODS: In vitro antioxidant activity was investigated using 2,2'-diphenyl-1-picrylhydrazyl (DPPH), fluorescence recovery after photobleaching (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. The antidiabetic and dermatoprotective effects were studied using enzyme inhibitory activities. RESULTS: Antioxidant tests showed that PLEO has the best activity (ranging from 29.64 ± 3.04 to 73.80 ± 3.96 µg/mL) compared to its main selected molecules (ranging from 74 ± 3.72 to 107.23 ± 5.03 µg/mL). The α-glucosidase and α-amylase assays demonstrated that the elements tested have a promising antidiabetic potential with IC50values ranging from 78.03 ± 2.31 to 116.03 ± 7.42 µg/mL and 74.39 ± 3.08 to 112.35 ± 4.92 µg/mL for the α-glucosidase and α-amylase assays, respectively, compared to the standard drug. For the tyrosinase test, we found that the EOs (IC50 = 57.72 ± 2.86 µg/mL) followed by limonene (IC50 = 74.24 ± 2.06 µg/mL) and α-pinene (IC50 = 97.45 ± 5.22 µg/mL) all exhibited greater inhibitory effects than quercetin (IC50 = 246.90 ± 2.54 µg/mL). CONCLUSIONS: Our results suggest that the biological activities of PLEO, as well as its main compounds, make them promising candidates for the development of new strategies aimed at improving dermatoprotection and treating diseases associated with diabetes mellitus and oxidative stress.

Molecular complexity of mammary glands development: a review of lactogenic differentiation in epithelial cells.

The mammary gland is a dynamic organ with various physiological processes like cellular proliferation, differentiation, and apoptosis during the pregnancy-lactation-involution cycle. It is essential to understand the molecular changes during the lactogenic differentiation of mammary epithelial cells (MECs, the milk-synthesizing cells). The MECs are organized as luminal milk-secreting cells and basal myoepithelial cells (responsible for milk ejection by contraction) that form the alveoli. The branching morphogenesis and lactogenic differentiation of the MECs prepare the gland for lactation. This process is governed by many molecular mediators including hormones, growth factors, cytokines, miRNAs, regulatory proteins, etc. Interestingly, various signalling pathways guide lactation and understanding these molecular transitions from pregnancy to lactation will help researchers design further research. Manipulation of genes responsible for milk synthesis and secretion will promote augmentation of milk yield in dairy animals. Identifying protein signatures of lactation will help develop strategies for persistent lactation and shortening the dry period in farm animals. The present review article discusses in details the physiological and molecular changes occurring during lactogenic differentiation of MECs and the associated hormones, regulatory proteins, miRNAs, and signalling pathways. An in-depth knowledge of the molecular events will aid in developing engineered cellular models for studies related to mammary gland diseases of humans and animals.

Comparative analysis of potential drug-drug interactions in a public and private hospital among chronic kidney disease patients in Khyber Pakhtunkhwa: A retrospective cross-sectional study.

INTRODUCTION: Chronic kidney disease (CKD) is a significant public health challenge due to its rising incidence, mortality, and morbidity. Patients with kidney diseases often suffer from various comorbid conditions, making them susceptible to potential drug-drug interactions (pDDIs) due to polypharmacy and multiple prescribers. Inappropriate prescriptions for CKD patients and their consequences in the form of pDDIs are a major challenge in Pakistan. AIM: This study aimed to compare the incidence and associated risk factors of pDDIs among a public and private sector hospital in Khyber Pakhtunkhwa, Pakistan. METHOD: A retrospective cross-sectional study design was conducted to compare pDDIs among public and private sector hospitals from January 2023 to February 2023. Patients profile data for the full year starting from January 1 2022 to December 302022, was accessed All adult patients aged 18 years and above, of both genders, who currently have or have previously been diagnosed with end-stage renal disease (ESRD) were included. For assessing pDDIs, patient data was retrieved and checked using Lexicomp UpToDate® for severity and documentation of potential drug-drug interactions. RESULTS: A total of 358 patients' data was retrieved (with n = 179 in each hospital); however, due to incomplete data, n = 4 patients were excluded from the final analysis. The prevalence of pDDIs was found to be significantly higher in private hospitals (84.7%) than in public hospitals (26.6%), with a p-value <0.001. Patients in the age category of 41-60 years (AOR = 6.2; p = 0.008) and those prescribed a higher number of drugs (AOR = 1.2; p = 0.027) were independently associated with pDDIs in private hospitals, while the higher number of prescribed drugs (AOR = 2.9; p = <0.001) was an independent risk factor for pDDIs in public hospitals. The majority of pDDIs (79.0%) were of moderate severity, and a significant number of patients (15.1%) also experienced major pDDIs, with a p-value <0.001. The majority of pDDIs had fair documentation for reliability rating in both public and private hospitals. CONCLUSION: The prevalence of pDDIs was higher among CKD patients at private hospitals, and most of the pDDIs were of moderate severity. A considerable number of patients also experienced major pDDIs. The risk of experiencing pDDIs was found to be higher in older patients and among those prescribed a higher number of drugs.

Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms.

Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.

Phytochemistry, quality control and medicinal uses of Saffron (Crocus sativus L.): an updated review.

Saffron, botanically known as Crocus sativus L., is renowned as the world's most expensive spice and has been utilized in various fields since ancient times. Extensive scientific research has been conducted on Crocus sativus (C. sativus), focusing on its phytochemical composition, diverse applications, and biological activities. C. sativus phytochemicals consist mainly of three compounds, namely crocin, picrocrocin, and safranal, which are responsible for most of its properties. Saffron is rich in bioactive compounds, more than 150 of which have been isolated. Owing to its unique composition and properties, saffron is used in various fields, such as the food industry, perfumery, cosmetics, pharmaceutics, and medicine. However, the high economic value of saffron makes it susceptible to adulteration and various fraudulent practices. To deal with this issue, a number of methods and techniques have been developed to authenticate and determine adulterants in saffron. This paper presents a bibliometric study of saffron based on the Web of Science database, analyzing 3,735 studies published between 2000 and 2021. The study also examined author participation and collaboration networks among countries. Production, transformation, chemical composition, methods of adulteration detection, uses, and health properties of saffron are also discussed.

Identification and optimization of TDP1 inhibitors from anthraquinone and chalcone derivatives: consensus scoring virtual screening and molecular simulations.

Virtual screening aims to identify and rank compounds with drug/lead-like properties based on their affinity for the protein target. We developed a methodology that integrates structure- and ligand-based screening approaches to enhance hit rates against the TDP1 protein within a database of anthraquinone and chalcone derivatives, followed by evaluation of prioritized compounds through molecular simulations. This technique is particularly useful for training set imbalances. Four screening methods were used: QSAR, pharmacophore, shape similarity, and docking. Each method was individually trained to score compounds, and the scores were fused to create parallel Z-score fusion. The QSAR models exhibited satisfactory R2 values (0.84 to 0.75), whereas the pharmacophoric and shape similarity models demonstrated excellent performance (ROC:0.82-0.88). Docking enrichment analysis identified 6N0D as the optimal TDP1 crystal structure (ROC = 0.73). Remarkably, the consensus scoring method surpassed other screening methods, achieving the highest ROC value of 0.98. Docking screening prioritized compounds with binding modes resembling the co-crystallized ligands, whereas MMGBSA, consensus, and docking produced dynamic simulations that were as stable as the co-crystallized ligands. Additionally, the QSAR-selected compounds exhibited binding modes similar to those of commercially available TDP1 inhibitors. In this study, a strong correlation was found between the inhibitory concentrations and binding energy values of commercialized TDP1 inhibitors, indicating that the top-ranked compounds are expected to have potent inhibitory effects in the nano-/micromolar range. The results of this study establish that consensus scoring can be used as an adaptable mainstay virtual screening methodology, pending subsequent experimental validation for affirmation.Communicated by Ramaswamy H. Sarma.

Hydroxychloroquine Toxicity in the Vital Organs of the Body: In Vivo Study.

BACKGROUND: Hydroxychloroquine (HCQ) toxicity can adversely affect vital organs, cause pathologic ocular damage, and can have direct cardiovascular effects. This study aims to identify the biochemical, hematological, and histological alterations of the vital organs associated with the effects of HCQ. METHODS: Male albino rats were exposed to the equivalent of HCQ therapeutic doses given to human patients being affected by malaria, lupus erythematosus, and COVID-19. The animal blood samples were subjected to hematological analysis, biochemical analysis, liver function tests, kidney function tests, and cardiac biomarkers. Liver, kidney, heart, spleen, and testis biopsies were subjected to histological examination. RESULTS: HCQ significantly lowered the values of erythrocytes, hemoglobin, hematocrit, platelets, leucocytes, and lymphocytes but significantly increased the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, alkaline phosphatase, lactate dehydrogenase, cholesterol, and chlorine ions. The renal tissues of HCQ-treated animals demonstrated glomerular fragmentation, partial atrophy degeneration, renal tubules hydropic degeneration, hyaline cast formation, and interstitial edema formation. Additionally, the heart exhibited myofiber necrosis, myolysis, wavy appearance, disorganization, and disarray. The testicular tissues also demonstrated spermatocyte degeneration, spermatogenic cell sloughing, testicular interstitial edema, and occasional spermatogenic arrest. Additionally, the spleen showed a decrease in the number and size of the white pulp follicles, a decrease in the number of apoptotic activity, and a decline in the number of T-rich cells. However, the red pulp demonstrated a diffuse decline in B rich-lymphocytes and macrophages. The liver was also the least affected but showed Kupffer cell hyperplasia and occasional hepatocyte dysplasia. CONCLUSIONS: The results indicate that chronic exposure to HCQ could alter the structures and functions of the vital organs.