Challenging Health Problems Worldwide Research Articles

Therapeutic Expedition of Luteolin against Brain-related Disorders: An Updated Review.

Brain-related disorders include neuroinflammation, neurodegenerative disorders, and demyelination, which ultimately affect the quality of life of patients. Currently, brain-related disorders represent the most challenging health problem worldwide due to complex pathogenesis and limited availability of drugs for their management. Further, the available pharmacotherapy accompanies serious side effects, therefore, much attention has been directed toward the development of alternative therapy derived from natural sources to treat such disorders. Recently, flavonoids, natural phytochemicals, have been reported as a treatment option for preventing brain aging and disorders related to this. Among these flavonoids, dietary luteolin, a flavone, is found in many plant products such as broccoli, chamomile tea, and honeysuckle bloom having several pharmacological properties including neuroprotective activities. Therefore, the objective of this paper is to compile the available literature regarding the neuroprotective potential of luteolin and its mechanism of action. Luteolin exerts notable anti-inflammatory, antioxidant, and antiapoptotic activity suggesting its therapeutic efficacy in different neurological disorders. Numerous in-vivo and in-vitro experiments have revealed that luteolin exhibits neuroprotective potential via up-regulating the ER/ERK, PI3AKT, Nrf2 pathways and down-regulating the MAPK/JAK2STAT and NFκB pathways. Taking into account of available facts regarding the neuroprotective efficacy of luteolin, the current study highlights the beneficial effects of luteolin for the prevention, management, and treatment of different neurological disorders. Thus, luteolin can be considered an alternative for the development of new pharmacophores against various brain-related disorders.

Prevalence of hypertension and related risk factors in older Chinese population: a meta-analysis.

Hypertension is the most challenging public health problem worldwide and seriously affects human health. To date, there are no epidemiological studies on the prevalence of and risk factors for hypertension among older people in mainland China. We conducted a meta-analysis of the prevalence and risk factors of hypertension among the older population in mainland China. We searched Chinese and English databases for Chinese and English literature on hypertension epidemiology published between 2000 and 2022, and hypertension data among the older population were extracted from the included literature. A meta-analysis was performed using a random-effects model (I2 > 50%) with 95% confidence intervals for the forest plots. Data were processed using RevMan 5.3. Forty-nine publications (with data from 84,429 samples) met the evaluation criteria and were included in this study. We found that the total prevalence of hypertension was 47%. The total prevalence rate of the older population in China from 2000 to 2010 was 50%, and the prevalence rate from 2011 to 2021 was 45%, with no significant differences. The total prevalence in Central China was the highest (59%). There was no significant correlation between the prevalence rate of the older population, sex, and urban or rural areas. Hypertension is common among the older population in China, and its control rate is low. Therefore, effective prevention and treatment measures, as well as education, should be formulated to improve the diagnosis and treatment of hypertension in the older population.

Hypolipidemic and Hypoglycemic Effects of Silybum marianum (L.) Gaertn.(Milk Thistle) Ethanol Seed Extract in Streptozotocin-induced Diabetes in Rats

Background: Metabolic syndrome (MS) is considered a challenging health problem worldwide. However, the search for alternative treatments to alleviate MS is lacking. Purpose: This study defines Silybum marianum (milk thistle) ethanol seed extract (SMESE) in terms of polyphenol and flavonoid content, antiglycation effect, α-amylase activity, and hypolipidemic and hypoglycemic effects in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: S. marianum seeds were collected, ground, and extracted with 80% ethanol. The α-amylase inhibitory activities of 10, 30, and 100 µg/mL SMESE were evaluated using spectrophotometric methods. The inhibitory activity of SMESE against advanced glycation end-product formation was evaluated using fluorescence spectrophotometry. In vivo, 48 Wistar male albino rats were used. Eight animals served as the normal control (group 1), and 40 rats were injected with 60 mg/kg STZ to induce diabetes. Diabetic rats were divided into five groups: diabetic control (group 2) and positive control that received the hypoglycemic reference drug metformin at 100 mg/kg (group 3). Groups 4, 5, and 6 were administered the seed extract orally at 30, 100, and 300 mg/kg, respectively. Body weight, serum glucose, lipid profile, and malondialdehyde (MDA) levels were measured weekly for five weeks after SMESE administration. Results: SMESE administration inhibited BSA glycation and α-amylase activity. In vivo, SMESE administration increased body weight (BW), decreased serum glucose levels, and reduced triglyceride, total cholesterol, low-density lipoprotein, very low-density lipoprotein, and MDA levels but increased high-density lipoprotein levels. Conclusion: Data indicate the beneficial hypoglycemic and antihyperlipidemic effects of SMESE, suggesting its potential use in controlling lipid metabolism.

Utilization, reimbursement, and price trends for Hepatitis C virus medications in the US Medicaid programs: 2001–2021

BackgroundHepatitis C Virus (HCV) remains a challenging health problem worldwide, with increasing incidence despite being curable with Direct Acting Antiviral (DAA) agents. ObjectiveThis study aimed to describe the utilization, reimbursement, and price trends of HCV treatments and evaluate the influence of treatment guidelines and policies. MethodsA retrospective, descriptive drug utilization study conducted using the outpatient pharmacy data extracted from the Centers for Medicaid and Medicare Services State Drug Utilization Data between 2001 and 2021. All HCV treatments approved in the US were included, conventional therapy (CT), and DAA agents. The annual secular trends were calculated for each medication's total number of prescriptions, reimbursements, and prices. The average reimbursement per prescription was calculated and utilized as a proxy of prices. The HCV treatment guideline and policies and legislation were evaluated overtime to measure the impact on the trends. ResultsDespite CT having a higher total utilization, DAA agents commanded significantly greater reimbursements, with 4.1 billion USD for CT and 19.45 billion USD for DAA agents. CT utilization increased rapidly and dominated the market until 2011, peaking at 379,696 prescriptions in 2003 but declining afterward. DAA agents' utilization increased rapidly in their first year: i.e., sofosbuvir reached 50,377 prescriptions with 1.3 billion USD in 2014, while ledipasvir/sofosbuvir reached 79,387 prescriptions with 2 billion USD in 2015. The average price per prescription was high for the DAA agents, like 24,992 USD for sofosbuvir and 22,787 USD for ledipasvir/sofosbuvir, compared to CT medications ribavirin, around 500 USD, and pegINF, around 3000 USD. The new DAA agents replaced CT, and initiating market competition among DAA agents. ConclusionThe introduction of multiple DAA agents slightly changed their prescription prices but remained high during the study period. The recent increase in HCV incidence cases indicates accessibility issues for costly and effective DAA agents, with treatment guidelines and policies playing a critical role in shaping these trends.

Study on material basis and anti-hypertensive metabolomics of different extraction methods of the Uncaria rhynchophylla Scrophularia Formula

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.

Localized Therapeutic Approaches Based on Micro/Nanofibers for Cancer Treatment.

Cancer remains one of the most challenging health problems worldwide, and localized therapeutic approaches based on micro/nanofibers have shown potential for its treatment. Micro/nanofibers offer several advantages as a drug delivery system, such as high surface area, tunable pore size, and sustained release properties, which can improve drug efficacy and reduce side effects. In addition, functionalization of these fibers with nanoparticles can enhance their targeting and therapeutic capabilities. Localized delivery of drugs and/or other therapeutic agents via micro/nanofibers can also help to overcome the limitations of systemic administration, such as poor bioavailability and off-target effects. Several studies have shown promising results in preclinical models of cancer, including inhibition of tumor growth and improved survival rates. However, more research is needed to overcome technical and regulatory challenges to bring these approaches to clinical use. Localized therapeutic approaches based on micro/nanofibers hold great promise for the future of cancer treatment, providing a targeted, effective, and minimally invasive alternative to traditional treatments. The main focus of this review is to explore the current treatments utilizing micro/nanofibers, as well as localized drug delivery systems that rely on fibrous structures to deliver and release drugs for the treatment of cancer in a specific area.

Clinical identification of expressed proteins in adrenal medullary hyperplasia detected with hypertension.

Hypertension remains a challenging public health problem worldwide, and adrenal gland-related diseases are one class of the major causes for secondary hypertension. Among them, one relatively rare pattern is adrenal hyperplastic hypertension caused by adrenal medullary hyperplasia (AMH), leading to excessive secretion of autonomic catecholamine. Given that the pathological changes of adrenal medulla are not well correlated to the onset and even severity of secondary hypertension, the molecular basis why some AMH patients are accompanied with hypertension remains unclear and is worth exploring. For this reason, this study aims at investigating differentially expressed proteins in clinical AMH tissue, with special focus on the potential contribution of these differentially expressed proteins to AMH development, in order to have a better understanding of mechanisms how AMH leads to secondary hypertension to some extent. To this end, AMH specimens were successfully obtained and verified through computed tomography (CT) and haematoxylin-eosin (HE) staining. Proteomic analyses of AMH and control tissues revealed 782 kinds of differentially expressed proteins. Compared with the control tissue, there were 357 types of upregulated proteins and 425 types of downregulated proteins detected in AMH tissue. Of interest, these differentially expressed proteins were significantly enriched in 60 gene ontology terms (P < 0.05), including 28 biological process terms, 14 molecular function terms, and 18 cellular component terms. Pathway analysis further indicated that 306 proteins exert their functions in at least one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Western blotting showed enhanced expression of phenylethanolamine N- methyltransferase (PNMT), myelin protein zero (MPZ), and Ras-related protein Rab-3C (RAB3C), and reduced expression of cluster of differentiation 36 (CD36) observed in AMH tissue in comparison with controls. Clinical AMH specimens display a different proteomic profile compared to control tissue. Of note, PNMT, MPZ, RAB3C, and CD36 are found to differentially expressed and can be potential targets for AMH, providing a theoretical basis for mechanistic exploration of AMH along with hypertension.

Antimicrobial Resistance of Salmonella Strains Isolated from Human, Wild Boar, and Environmental Samples in 2018-2020 in the Northwest of Italy.

Antimicrobial resistance is one of the most challenging public health problems worldwide, and integrated surveillance is a key aspect in a One Health control strategy. Additionally, Salmonella is the second most common zoonosis in Europe. We aimed to investigate the circulation of Salmonella strains and their related antimicrobial resistance in human, environmental, and wild boar samples from the northwest of Italy, from 2018 to 2020, to obtain a more comprehensive epidemiological picture. Salmonella Typhimurium 1,4,[5],12:i:-, S. Veneziana and S. Newport were the most common serotypes occurring in humans, the environment, and wild boar, respectively. Antimicrobial resistance was rather common in Salmonella isolates, with those from human displaying the highest degree of resistance against sulfadiazine-sulfamerazine-sulfamethazine (&gt;90% of resistance). Moreover, resistance against azithromycin were exclusively observed in environmental samples, while only 7.7% (95% CI = 1.6-20.8) of wild boar isolates experienced resistance against trimethoprim-sulfamethoxazole. Multidrug resistance concurrently involved up to seven antimicrobial classes in human isolates, including third-generation cephalosporins and fluoroquinolones. Salmonella Typhimurium in humans and serotypes Goldcoast and Rissen from environmental sources showed the highest levels of resistance. This study shows diverse antimicrobial resistance patterns in Salmonella strains isolated from different sources and gives a broad picture of antimicrobial resistance spread in wild animals, humans, and the environment.

Drug resistant bacterial contamination of inanimate surfaces, equipment and health care workers in ICU of a tertiary care Hospital in North India

ICU-acquired infections are a challenging health problem worldwide as the patient’s immunity is already compromised and these infections are usually caused by MDR pathogens. In ICUs inanimate surfaces and equipment may be contaminated by bacteria. Cross-transmission of microorganisms from inanimate surfaces may have a significant role for ICU-acquired infections. Contamination may result from HCWs hands or by direct patient shedding of bacteria. This study was conducted to determine the rate of bacterial contamination on environmental surfaces and health care workers of ICU our hospital. Swabs from healthcare workers and surrounding environmental surfaces were collected randomly from Adult Intensive care units. Bacterial isolates were identified by standard microbiological techniques. Antibiotic sensitivity testing was performed by Kirby Bauer disc diffusion method and data was analyzed. A total of 35 samples were collected, of which 29 (82.8 %) samples yielded positive bacterial growth. Of these 29-positive growth, 10 (34.1%) were from hand swabs of HCWs, 10(34.1%) were from nasal swabs and 9(31.0%) were from environment. Seven different bacterial isolates were identified. Coagulase Negative Staphylococcus (CONS) 10(28.5%), MRSA 5(14.2%) and Klebsiella spp 5(14.2%) accounted for majority of the isolates followed by MSSA 3(8.5%), Pseudomonas spp 1(2.8%), E.coli 1(2.8%) and ASB 4(11.4%).

ANALISIS PERBANDINGAN KLASIFIKASI CITRA MYCROBACTERIUM TUBERCULOSIS

Tuberculosis (TB) is an infectious disease that remains a challenging health problem worldwide. This disease is caused by rod-shaped bacteria called Mycobacterium tuberculosis. These bacteria usually affect the lungs but can also spread to other parts of the body such as the eyes, bones and blood vessels. It was reported that around. 4.74 million new TB cases were identified and around eight hundred thousand people died from TB, during 2015 in Southeast Asia. In this study, color image segmentation techniques were carried out using classification methods by comparing several methods including Logistic Regression, Linear Discriminant Analysis, K- Neighbors Classifier, Decision Tree Classifier, Random Forest Classifier, Gaussian NaiveBayes, and Support Vector Machine. In the final stage it is known that the validation test on the Random Forest Classifier produces the highest value of 86.04%.

Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.

Dietary adherence and associated factors among hypertensive patients in Bahir Dar city Administration, Ethiopia, 2020

IntroductionHypertension is considered one of the most challenging public health problems worldwide. Adherence to the recommended diet has a key role to reduce uncontrolled hypertension and hypertension-related complications. A study on dietary adherence among hypertensive patients and associated factors are limited in Ethiopia. So, this study aimed to assess dietary adherence and associated factors among hypertensive patients in Bahir Dar city governmental hospitals, Bahir Dar, Ethiopia. MethodA cross-sectional study was conducted at Bahir Dar city governmental hospitals from February- March 2020. Proportional allocation and systematic random sampling techniques were used to select 386 individuals with hypertension. The logistic regression model was used to assess the association between predictors and dietary adherence. The association was interpreted using the odds ratio and 95% confidence interval. ResultIn this the proportion of dietary adherence was 32.8 % (CI: 28.0, 37.6). Educational level college and above (AOR = 3.0, CI = 1.26, 7.08), received nutritional education (AOR = 1.9, CI = 1.05, 3.62), knowledgeable about hypertension (AOR = 2.5, CI = 1.36, 4.58), who had no co-morbidities (AOR = 2.8, CI = 1.49, 5.20), who lived two to four years with hypertension (AOR = 2.4, CI = 1.17, 5.07), and who had strong social support (AOR = 7.1, CI = 2.85, 17.46) had significantly association with dietary adherence. ConclusionThis study demonstrated that participants have low adherence to dietary recommendation Therefore, availed a social network of family and friends; providing dietary education to address the participants’ knowledge of hypertension, promote survival skill to new diagnosed and considered co-morbidities are an integral part of overall health in people with hypertension.

The Effect of Diabetes Mellitus on IGF Axis and Stem Cell Mediated Regeneration of the Periodontium

Periodontitis and diabetes mellitus (DM) are two of the most common and challenging health problems worldwide and they affect each other mutually and adversely. Current periodontal therapies have unpredictable outcome in diabetic patients. Periodontal tissue engineering is a challenging but promising approach that aims at restoring periodontal tissues using one or all of the following: stem cells, signalling molecules and scaffolds. Mesenchymal stem cells (MSCs) and insulin-like growth factor (IGF) represent ideal examples of stem cells and signalling molecules. This review outlines the most recent updates in characterizing MSCs isolated from diabetics to fully understand why diabetics are more prone to periodontitis that theoretically reflect the impaired regenerative capabilities of their native stem cells. This characterisation is of utmost importance to enhance autologous stem cells based tissue regeneration in diabetic patients using both MSCs and members of IGF axis.

Deranged Lipid Profiles and Hepatocellular carcinoma: Clinical Significance and Association

Background: The increasing incidence of hepatocellular carcinoma (HCC) is a challenging health problem worldwide with poor prognosis and limited treatment options. The association between metabolic factors and HCC has been documented, however, there is a shortage of data about this association in our locality. Therefore, we aimed to determine the pattern of lipid profile in cirrhotic patients with HCC and investigate the association between dyslipidemia and HCC. Method: In this case-control hospital-based study, serum lipid profile [total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL)] was determined in 100 patients with cirrhosis and 100 patients with cirrhosis and HCC. Multivariate analysis of HCC risk factors was done. Results: Metabolic syndrome, hypertriglyceridemia, hypercholesterolemia, high LDL, and combined dyslipidemia were significantly more frequent in HCC patients than non-HCC patients. Low HDL and dyslipidemia were significantly associated with the late HCC stages and LDL levels were significantly correlated with α-fetoprotein levels. There was a tendency towards increasing the values of the other lipid parameters in advanced stages. Metabolic syndrome and combined dyslipidemia were associated with HCC risk. Conclusion: Deranged lipid profiles were common in HCC patients. Metabolic syndrome and combined dyslipidemia could be potential risk factors for HCC and may offer a useful strategy for risk stratification; thus, their control can reduce the HCC burden.

Identifying the predictors of Covid-19 infection outcomes and development of prediction models

BackgroundThe infection of Corona Virus Disease (Covid-19) is challenging health problems worldwide. COVID-19 pandemic is spreading all over the world with the number of infected cases increased to 54.4 million with 1.32 million deaths. Different types of statistical models have been developed to predict viral infection and multiple studies have compared the performance of these predictive models, but results were not consistent. This study aimed to develop and provide easy to use model to predict the Covid-19 infection severity in the patients and to help understanding the patient’s condition. MethodsThis study analyzed simulated data obtained from the large database for 340 patients with an active Covid-19 infection. The study identified predictors of Covid-19 outcomes that may be measured in two different ways: the total T-cell levels in the blood with T-cell subsets and number of cells in the blood infected with virus. All measures are relatively unobtrusive as they only require a blood sample, however there is a significant laboratory cost implications for measuring the number of cells infected with virus. This study used methodological approach using two different methods showing how multiple regression and logistic regression can be used in the context of Covid-19 longitudinal data to develop the prediction models. ResultsThis study has identified the predictors of Covid-19 infection outcomes and developed prediction models. In the regression model of Total_T Cell, the predictors BMI, comorbidity and Total_Tcell were all associated with increased levels of infection severity (p < 0.001). For BMI, the mean % of unhealthy cells increased by 0.42 (95% CI 0.24 to 0.60) and comorbidity predictor has on average 8.3% more unhealthy liver cells than without comorbidity (95% CI — 2.9%–1.29%). The results of multivariate logistic regression model predicting the Covid-19 Infection severity were promising. The significant predictors were observed such as Age (OR 0.95, p = 0.02, 95% CI: 0.91–0.99), Helper T_cells (OR O.93, p = 0.03, 95% CI: 0.87–0.99), Basic_Tcell (OR 1.11, p = 0.001, 95% CI: 1.06–1.71) and Comorbidity (OR 0.41, p = 0.05, 95% CI: 0.16–1.07). ConclusionsIn this study recommendation has been provided to clinical researchers on the best way to use the various Covid-19 infections measures along with identifying other possible predictors of Covid-19 infection. It is imperative to monitor closely the T-cell subsets using prediction models that might provide valuable information about the patient’s condition during the treatment process.

Investigation of the Effects of Trehalose on Glycemic Indices in Streptozotocin-Induced Diabetic Rats.

Diabetes is a chronic metabolic disorder with considerable morbidity and mortality because of its associated complications that has become a challenging health problem worldwide. Trehalose (mycose) is a nonreducing disaccharide with a unique therapeutic potency without adverse effects, which has been found to improve glucose metabolism and homeostasis in different diabetes models. We hypothesized that trehalose can reduce blood glucose and improve insulin sensitivity. We have conducted this study to evaluate the effect of trehalose on glycemic indices in streptozotocin (STZ)-induced diabetic rats. Fourteen diabetic rats were randomly assigned in two treatment groups (seven rats per group) that received trehalose at a dose of 1.5g/kg/day via oral gavage and a dose of 45mg/kg/day via intraperitoneal (i.p.)injection. Three control groups, including a positive control, diabetic control (DC), and nondiabetic rats as a normal control group (NC), received metformin (200mg/kg/day), normal saline, and citrate buffer, respectively. The levels of fasting blood glucose (FBG) were measured at baseline (week 0) and after 4weeks of treatment. Moreover, an oral glucose tolerance test (OGTT) was performed at the end of the study to determine glucose tolerance. The results showed that FBG levels were significantly decreased by -66% (-221±65mg/dL, p=0.01), -40% (-114±46mg/dL, p=0.02), and -72% (-191±68mg/dL, p=0.01) in trehalose-oral, trehalose-i.p., and metformin groups, respectively, after 4weeks of administration. Evaluating the results of glucose tolerance test and analysis of corresponding areas under the glucose curve (AUCglucose) over 180 min indicated that glucose tolerance was significantly improved in the trehalose-i.p. group (p=0.03) compared to DC group. Our findings suggested that trehalose administered via i.p. route might reduce FBG levels and improve glycemic control in STZ-induced diabetic rats.

Epigenetic regulation by polyphenols in diabetes and related complications

Diabetes mellitus (DM) is a chronic metabolic disorder and one of the most challenging health problems worldwide. Left untreated, it may progress causing serious complications. Genetics, epigenetics, and environmental factors are known to play an overlapping role in the pathogenesis of DM. Growing evidence suggests the hypothesis that the environment induces changes in the early phases of growth and development, influencing health and disease in the adulthood through the alteration in genetic expression of an individual, at least in part. DNA methylation, histone modifications and miRNAs are three mechanisms responsible for epigenetic alterations. The daily diet contains a number of secondary metabolites, with polyphenols being highest in abundance, which contribute to overall health and may prevent or delay the onset of many chronic diseases. Polyphenols have the ability to alter metabolic and signaling pathways at various levels, such as gene expression, epigenetic regulation, protein expression and enzyme activity. The potential efficacy of polyphenolic compounds on glucose homeostasis has been evidenced from in vitro, in vivo and clinical studies. The present review is designed to focus on epigenetic regulation exerted by polyphenolic compounds in DM and their complications, as well as to summarize clinical trials involving polyphenols in DM.

Impact of Family Medicine Training on the Quality of Care for patients of diabetes in Saudi Arabia

IntroductionDiabetes mellitus (DM) is one of the challenging health problems worldwide. Primary care centers manage and treat most of DM cases. Diabetes requires ongoing, and evidence-based health care which should be provided by highly qualified physicians. AimThis study aims at evaluating the Family Medicine training efficacy on the quality of care for diabetic patients. MethodologyThis is a cross-sectional study conducted among patients with DM at the AlJafer training center situated in AlAhssa, Saudi Arabia. The data of diabetic patients who were followed up initially with general practitioners (GPs) and later with family physicians (FPs) collected from the patients’ electronic files. Clinical parameters including HbA1c, blood pressure, total cholesterol, LDL, and statin, aspirin initiation measured during initial visits and follow-ups to compare the quality of diabetic care between the two groups (FPs vs. GPs). All statistical analyses carried using SPSS version 21. ResultsEighty-three patients were included in the study. Regarding the measurement process, FPs more likely to measure HbA1c twice a year than GPs (P:<0.001). The number of patients with HbA1c level >8% decreased significantly during the period of follow-up with FPs (P:<0.001). Furthermore, a significant number of patients meet the BP target ≤130/85 during the follow-up period with FPs. The statin initiation is substantially achieved more by FPs (P < 0.001). ConclusionFamily medicine training has a significant influence on the clinical outcomes of patients with DM. This study’s findings suggest that FPs ensure a better quality of care in terms of clinical and process measures.

Cationic RuII Cyclopentadienyl Complexes with Antifungal Activity against Several Candida Species.

Fungal infections, including those caused by antifungal-resistant Candida, are a very challenging health problem worldwide. Whereas different ruthenium complexes were previously studied for their anti-Candida potential, Ru-cyclopentadienyl complexes were overlooked. Here, we report an antifungal activity assessment of three Ru-cyclopentadienyl complexes with some insights into their potential mode of action. Among these complexes, only the cationic species [Ru-ACN]+ and [Ru-ATZ]+ displayed a significant antifungal activity against different Candida strains, notably against the ones that did not respond to one of the most currently used antifungal drugs fluconazole (FCZ). However, no apparent activity was observed for the neutral species, Ru-Cl, thus indicating the important role of the cationic backbone of these complexes in their biological activity. We suggest that reactive oxygen species (ROS) generation might be involved in the mechanism of action of these complexes as, unlike neutral Ru-Cl, [Ru-ACN]+ and [Ru-ATZ]+ could generate intracellular concentration-dependent ROS. We also observed a correlation between the ruthenium cellular uptake, ROS generation and fungal growth inhibitory activity of the compounds. Furthermore, docking simulations showed that the CYP51 enzyme can form more energetically favorable complexes with [Ru-ATZ]+ than fluconazole (FCZ); this suggests that CYP51 inhibition could also be considered as a potential mode of action.

Injectable Enzyme-Based Hydrogel Matrix with Precisely Oxidative Stress Defense for Promoting Dermal Repair of Burn Wound.

Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol-Fe3+ coordination hydrogel (MICH) matrix, is engineered to promote burn-wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of "Fe-superoxide dismutases," small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn-wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re-epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn-wound care and other disease therapy induced by oxidative stress.