Association Between Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) With Diabetic Retinopathy in Type 2 Diabetic Patients.

Diabetic retinopathy (DR) is one of the main causes of blindness worldwide, but an effective screening is challenging due to limited available retina specialists. Finding novel biomarkers could help clinical decision in prioritizing ophthalmological consultation in patients at risk of developing severe DR. This study aims to investigate the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the presence and severity of DR in patients with T2DM. A retrospective study was performed on 90 patients with T2DM admitted in the Ophthalmology Clinic, Emergency University Hospital Bucharest in Bucharest, Romania, between March 2022 and March 2023, for routine cataract surgery. The cases were divided into three groups according to the severity of DR: no DR (noDR), non-proliferative diabetic retinopathy (NPDR), and proliferative DR (PDR) groups. NLR values raised significantly in the PDR group, no DR group (p = 0.003), and NPDR group (p = 0.026), while PLR values did not differ statistically significant among the groups (p = 0.059). No difference in terms of age, sex, HbA1C, and comorbidities were observed. In the multivariate analysis, the NLR (OR = 2.01, [1.29; 3.14], p = 0.0019) and diabetic nephropathy (OR = 3.84, [1.23; 11.98], p = 0.0203) were associated with higher rates of PDR. NLR may be a promising tool in the risk stratification of T2DM patients with DR.

[Corrigendum] Effect of the combination of Lactobacillus acidophilus (probiotic) with vitamin K3 and vitamin E on Escherichia coli and Staphylococcus aureus: An in vitro pathogen model and metastasis in vivo.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 3B on p. 7 showing the results of immunohistochemistry staining experiments, the data panels shown for the 'L+K' and 'EC+E+K' groups were strikingly similar, such that they appeared to be derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that Fig. 3B was inadvertently assembled incorrectly; specifically, the data shown for the 'L+K' group in Fig. 3B were featured incorrectly. The revised version of Fig. 3, now containing the correct data for the 'L+K' experimental group in Fig. 3B is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 27: 119, 2023; DOI: 10.3892/mmr.2023.13006].

Effect of the combination of Lactobacillus acidophilus (probiotic) with vitamin K3 and vitamin E on Escherichia coli and Staphylococcus aureus: An in vitro pathogen model.

The gut microbiota plays a key role in maintaining health and regulating the host's immune response. The use of probiotics and concomitant vitamins can increase mucus secretion by improving the intestinal microbial population and prevent the breakdown of tight junction proteins by reducing lipopolysaccharide concentration. Changes in the intestinal microbiome mass affect multiple metabolic and physiological functions. Studies on how this microbiome mass and the regulation in the gastrointestinal tract are affected by probiotic supplements and vitamin combinations have attracted attention. The current study evaluated vitamins K and E and probiotic combinations effects on Escherichia coli and Staphylococcus aureus. Minimal inhibition concentrations of vitamins and probiotics were determined. In addition, inhibition zone diameters, antioxidant activities and immunohistochemical evaluation of the cell for DNA damage were performed to evaluate the effects of vitamins and probiotics. At the specified dose intervals, L. acidophilus and vitamin combinations inhibit the growth of Escherichia coli and Staphylococcus aureus. It could thus contribute positively to biological functions by exerting immune system­strengthening activities.

Gut Microbiota Dysbiosis in Diabetic Retinopathy-Current Knowledge and Future Therapeutic Targets.

Diabetic retinopathy is one of the major causes of blindness today, despite important achievements in diagnosis and therapy. The involvement of a gut-retina axis is thought to be a possible risk factor for several chronic eye disease, such as glaucoma, age-related macular degeneration, uveitis, and, recently, diabetic retinopathy. Dysbiosis may cause endothelial disfunction and alter retinal metabolism. This review analyzes the evidence regarding changes in gut microbiota in patients with DR compared with diabetics and healthy controls (HCs). A systematic review was performed on PubMed, Web of Science, and Google Scholar for the following terms: "gut microbiota" OR "gut microbiome" AND "diabetic retinopathy". Ultimately, 9 articles published between 2020 and 2022 presenting comparative data on a total of 228 T2DM patients with DR, 220 patients with T2DM, and 118 HCs were analyzed. All of the studies found a distinctive microbial beta diversity in DR vs. T2DM and HC, characterized by an altered Firmicutes/Bacteroidetes ratio, a decrease in butyrate producers, and an increase in LPS-expressing and pro-inflammatory species in the Bacteroidetes and Proteobacteria phyla. The probiotic species Bifidobacterium and Lactobacillus were decreased when compared with T2DM. Gut microbiota influence retinal health in multiple ways and may represent a future therapeutic target in DR.

New method for risk assessment in environmental health: The paradigm of heavy metals in honey.

The release of heavy metals into the natural environment creates problems due to their persistence. They can accumulate in the food chain presenting a dangerous sign for ecosystems and human health. The metals in honey could be of agrochemical or industrial origin. Regular consumption of honey and bee products contaminated with various pollutants in high concentrations can cause serious health problems due accumulation of toxic substances in the body. In the current study, we aimed to determine the concentrations of chromium, cadmium, zinc, copper, lead and nickel in four types of honey (linden, acacia, rapeseed and polyfloral honey) and soil collected from three regions with different degrees of pollution. For the risk characterization, we used a new methodology that calculated the corrected estimated daily intake and the source hazard quotient for each metal and the adversity-specific hazard index. There was a strong influence of the degree of environmental pollution on the level of contaminants in the honey samples. In the case of a single chemical assessment, an HQ above 10 was obtained for Cd in linden, rapeseed and polyfloral honey from area 1 and an HQ above 1 was obtained for Cd in the other honey samples from the 3 areas, for Cu in all honey samples from all the 3 areas, for Pb in linden, rapeseed and polyfloral honey from area 1 and for Cr in linden honey for area 2. HIA calculated as a sum of all HQS of heavy metals in food reveals an increase and moderate risk for nephrotoxicity, bone demineralisation, cardiotoxicity, developmental toxicity, small decrease in body weight or body weight gain after consumption of honey impurified with heavy metals. A strict monitorization of heavy metals in honey samples from farmers should be done in order to protect the consumers.

Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection.

Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV's elimination that included a 65 percent reduction in mortality and an 80 percent reduction in newly infected cases by 2030. This study is a follow-up evaluation of 80 patients who received interferon-free treatment with direct-acting agents (DAA) for chronic HCV infection between the second half of 2017 and the end of 2018. They were assessed using a FibroMax test prior to DAA administration. Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. After treatment, all 80 patients in this study achieved an SVR (sustained virologic response), and the FibroMax test was performed three years later. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients.

Heavy metal and pesticide levels in dairy products: Evaluation of human health risk.

Cattle milk's health benefits can be compromised by the presence of contaminants. The levels of cadmium, copper, lead and zinc, and residues of dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), dichlorodiphenyltrichloroethane (DDT) were determined in soil, milk and cheese samples collected from cow farms from 3 Romanian areas with industrial and agriculture tradition. A new methodology was applied for the determination of the corrected estimated daily intake (cEDI) corresponding to the aggregate dietary exposure. For the risk assessment, we calculated the source hazard quotient (HQs) for each contaminant and the adversity specific hazard index (HIA). Cadmium, copper, lead and zinc, and the sum of DDT levels in soil samples were below maximum residue levels (MRLs). The MRLs of lead and DDD were exceeded in milk and cheese samples from all the 3 areas. The MRLs of copper and zinc were exceeded in cheese samples from area 2 and 3. HQs >10 for lead indicates increased risk, while HQ > 1 for copper and sum of DDT indicates moderate risk for both milk and cheese. By calculating the HIA, we identified a moderate and increase risk for nephrotoxicity, hepatotoxicity, hematotoxicity, cardiotoxicity and reproduction toxicity after consumption of the dairy products from the 3 areas.

Recent advances, approaches and challenges in targeting pathways for potential COVID-19 vaccines development.

During the COVID-19 pandemic in a modern era, there is a global consensus on the need for the rapid development of a vaccine against SARS-CoV-2 for effective and sustainable control. Developing these vaccines is fundamental to public health. This urgent need is supported by the scientific explosion in structural and genomic biology that facilitates the urgent development of an ideal COVID-19 vaccine, using new pathways to facilitate its large-scale development, testing, and manufacture. Here, we summarize the types of COVID-19 candidate vaccines, their current stage in early testing in human clinical trials, and the challenges for their implementation.

Adverse and hormetic effects in rats exposed for 12 months to low dose mixture of 13 chemicals: RLRS part III.

The aim of the current study was to evaluate the effects of a mixture of thirteen common chemicals on rats, after a one-year exposure to doses around the acceptable daily intake (ADIs), using blood and urinary tests. The influence of low doses of the mixture on weight gain, water consumption, feed consumption and feed efficiency, biochemistry parameters, haematological parameters, blood lymphocytes subsets, serum inflammation profile and urine parameters was evaluated. Our mixture caused a moderate monotonic increase of the males' appetite and a non-monotonic increase of anabolism and a monotonic increase of appetite for the females. Regarding biochemical parameters, the exposure to the test mixture caused non-monotonic increases of AST and ALT, a decrease of PChE in males and plausibly a monotonic biliary obstruction in both sexes. Monocytes significantly increased in low dose groups of both sexes. A significant decrease of all the lymphocytes subclasses and an increased expression of TNF-α protein associated with an increased expression of IFN-γ protein observed in various groups. It became apparent that after twelve months of exposure very low doses of the tested mixture had both non-monotonic and monotonic harmful effects on different levels on rats.

Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems.

The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action.

CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.

The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases.

Therapeutic potential of certain drug combinations on paclitaxel-induced peripheral neuropathy in rats.

BACKGROUND AND AIMS: Experimental research and clinical data support the potential combination therapy for the treatment of neuropathic pain. We aimed to investigate the analgesic effect of the following associations: gabapentin + etifoxine; tramadol + etifoxine; gabapentin + tramadol, in an experimental model of peripheral neuropathy induced by paclitaxel. MATERIALS AND METHODS: Neuropathy was induced in male Wistar rats by the daily administration of 2 mg÷kg body weight (bw) paclitaxel intraperitoneally, four days in a row. Analgesics were given concomitantly with paclitaxel, in the following doses: tramadol 15 mg÷kg bw, etifoxine 100 mg÷kg bw, gabapentin 300 mg÷kg bw. Tactile allodynia and mechanical hyperalgesia were assessed using the Dynamic Plantar Aesthesiometer apparatus (Ugo Basile). After 18 days of treatment, the brain and liver tissue susceptibility to lipid peroxidation was evaluated and the sciatic nerve histological examination of the effect on myelin fibers was performed. RESULTS AND CONCLUSIONS: Experimental data have shown a strong analgesic effect of these three tested combinations expressed mainly by the statistically significant increased maximum response time, both in the assessment of allodynia and hyperalgesia. The gabapentin + tramadol combination lead to the maximum analgesic effect, immediately after the discontinuation of paclitaxel (44.94%, p<0.0001) and throughout the study. The treatment associated with tramadol caused a reduction in lipid peroxidation in the brain as compared to paclitaxel group. Combination therapy showed reduced damage to myelinated fiber density in the sciatic nerve. The drug combinations used in the experiment showed therapeutic potential in the fight against neuropathic pain induced by the administration of taxanes.

Pharmacological management of non-alcoholic fatty liver disease: Atorvastatin versus pentoxifylline.

In this study, we aimed to evaluate the efficacy of pentoxifylline and atorvastatin in the treatment of non-alcoholic fatty liver disease (NAFLD). The study included 98 patients with histologically confirmed NAFLD divided into 2 groups as follows: group I (57 dyslipidemic patients, receiving atorvastatin 20 mg/day and group II (41 non-dyslipidemic patients, treated with pentoxifylline, 800 mg/day). The present study was conducted for a mean of 32.8±3.4 weeks. For all patients, we determined the body mass index, a liver biopsy was performed, and we measured the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total cholesterol (TC) and triglycerides (TG) at the beginning and at the end of the study period. The NAFLD activity score (NAS) was used to evaluate the liver biopsies for steatosis, fibrosis and necroinflammation. The patients in group I exhibited a considerable reduction in ALT, AST, GGT, TC, AP and TG levels (P<0.0001). Histologically, there were no changes in fibrosis and necroinflammation, although the extent steatosis was reduced. The improvement in the ALT, AST and GGT values (P<0.05) in group II were similar to those in group I; however, no statistically significant decrease was noted in the levels of ALP, TC and TG in this group. Our results thus demonstrated that atorvastatin attenuated steatosis and improved liver function parameters in patients with NAFLD associated with dyslipidemia. Similar results were obtained in the non-dyslipidemic patients administered pentoxifylline.

A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian perspective.

Physicians often come across with cases of vitamin K antagonists-dependent coagulopathy for reasons such as accidental use of the vitamin K antagonists (VKA), excessive administration of prescribed anticoagulants of indirect action or not reported administration of vitamin K antagonists due to memory impairment and/or other mental disorders, even deliberate use thereof (attempt to murder or suicide). Rodenticide-poisoning (coumarins, warfarins) via food or occupational accidents are difficult to diagnose. This article discusses different types of acquired vitamin K-dependent coagulopathy. Differential diagnosis is primarily based on patient statements before additional causes of vitamin K deficiency are explored. Even when pathological vitamin K deficiency is not determined, appropriate and urgent medical treatment is necessary: administration of fresh frozen plasma or concentrated factors of the prothrombin complex, administration of vitamin K remedies along with symptomatic therapy. With early diagnosis and prescription of appropriate therapy, prognosis is favorable. Reasons for vitamin K antagonists-dependent coagulopathy cases.

Pharmacotoxicological screening on new derivatives of beta-phenylethylamine, potential agonists of beta3-adrenergic receptors.

BACKGROUND AND AIMS: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity. Therefore, new compounds were synthesized starting from beta-phenylethylamine nucleus and substituted in various positions, for possible antidiabetic and÷or antiobesity action. MATERIALS AND METHODS: In the present research, the antidiabetic action of newly synthesized compounds was investigated on an experimental model of alloxan-induced diabetes, administered in dose of 130 mg÷kg body weight (bw), intraperitoneally (i.p.). After 14 days of treatment, glycemia and enzymes involved in homeostasis of glucose metabolism, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6Pase) and hexokinase were determined. Animals were then euthanized and histopathology examinations were performed on harvested liver, kidney, spleen and brain in order to document pathological changes induced by alloxan-induced diabetes and÷or by tested compounds. RESULTS AND CONCLUSIONS: Glycemia in animals treated with the tested compounds decreased statistically significant for groups C2 and C3 (-42.13% and -37.2%, respectively), compared to diabetic control group. C2 was also the compound to favorably modify the dynamics of determined enzymes, together with the display of very good safety profile supported by minor, non-significant, histopathological changes.

Behavioral and molecular effects of prenatal continuous light exposure in the adult rat.

Disruption of the maternal environment during pregnancy leads to behavioral changes and diseases in the adult offspring. To explore the influence of prenatal continuous light exposure (PCLE) on the adult offspring, we exposed pregnant Wistar rats to constant light during late gestation. Adult PCLE offspring showed an anxiety-like behavior and impairment of short-term memory in different tests. Measurements in the whole brain homogenates from newborn and adult offspring indicated decreased melatonin and serotonin levels and increased reactive oxygen species level in PCLE offspring. Further, we determined melatonin-, serotonin-, oxidative stress-, apoptosis-, and circadian system-related genes expression in different brain areas of adult offspring. The serotonin reuptaker Slc6a4 displayed a decreased expression in the prefrontal cortex of PCLE group. The circadian rhythm-related gene Rora was upregulated in the amygdala of PCLE offspring. Our results point to adverse behavioral effects of PCLE on adult offspring, involving serotonin and melatonin signaling dysregulation, increased chronic oxidative stress, and altered gene expression.