Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility.

The advent of highly active antiretroviral therapy (HAART) in 1996 has markedly enhanced the life expectancy of people living with HIV (PLWH), largely due to the effectiveness of reverse transcriptase inhibitors (RTIs). These drugs target the reverse transcriptase enzyme, crucial for the HIV virus to convert its RNA into DNA within host cells, effectively disrupting the viral replication process. This action reduces the patient's viral load, helping preserve immune function and prevent progression to AIDS. Consequently, the predominant causes of mortality among individuals living with HIV have transitioned from opportunistic infections and AIDS-related cancers to liver disease and cardiovascular complications. Liver damage in PLWH could arise from multiple sources including co-infections, chronic substance use, and notably, antiretroviral therapy itself, which can be hepatotoxic. This review highlights the risks of hepatic damage associated with nucleoside and non-nucleoside RTIs and underscores the variability in hepatotoxicity risks among different drugs. It emphasizes the necessity for regular monitoring of liver health in PLWH and adjusting antiretroviral regimens to minimize liver fibrosis risk. This risk is particularly pronounced in patients who associate the infection with hepatitis B or C virus, where the potential for hepatotoxicity significantly increases.

The current study aimed to assess the possible endocrine disruptor effects on rat mammary tissue and reproductive organs during pregnancy and lactation when exposed to low doses of glyphosate and its combination with 2,4-dichlorophenoxyacetic acid (2,4-D) and dicamba. The study involved the exposure of pregnant Wistar rats to various regulatory-relevant doses of glyphosate, ranging from gestational day 6 until fine of the lactation period. Glyphosate doses corresponded to the European Union's glyphosate-acceptable daily intake (ADI; 0.5mg/kg bw/day) and no observed adverse effect level (NOAEL; 50mg/kg bw/day). The dose of the mixture of glyphosate, dicamba, and 2,4-D was at the European Union ADI for each herbicide namely 0.5, 0.002, and 0.3mg/kg bw/day, respectively. In the animals exposed to glyphosate NOAEL serum estradiol levels were increased compared to untreated animals, along with an upregulation of TNF-?, MMP-2, and MMP-9 as measured in mammary gland homogenates compared to non-treated animals. Moreover, in this group, a focally acute inflammatory infiltrate was observed in the mammary gland. Our study showed that short-term exposure to glyphosate at doses that are set as safe by regulators and thus without risk corroborated with a particular physiological state as gestation and lactation, can give rise to inflammatory changes in breast tissue in rats. These findings support the need for further evaluation of glyphosate and mixtures of glyphosate with other pesticides for public health protection, especially for those categories vulnerable to the potential endocrine disruptor properties of these pesticides such as pregnant women, newborns, and children.

The study aimed to determine liver fibrosis in human immunodeficiency virus (HIV) positive individuals using transient elastography (FibroScan®), Fibrosis-4 (FIB-4) score, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) in the HIV Department from Infectious Diseases Hospital “Victor Babeș” Craiova, Romania. Of the analyzed HIV-positive subjects (n = 161), 93 (57.76%) had HIV mono-infection, and 68 (42.24%) had Hepatitis B Virus (HBV) co-infection. The prevalence of advanced liver fibrosis was higher (F2: 11.76% and F3: 13.24%, F4: 4.41%) in the HIV-HBV co-infected group compared to the HIV mono-infected group. The univariate and multivariate analysis identified HBV co-infection (OR = 5.73) male sex (OR = 5.34), serum aspartate amino-transferase levels (Pearson’s rho = 0.273), low platelet count (Pearson’s rho = −0.149) and erythrocyte sedimentation rate (OR = 1.030) as risk factors for the presence of liver fibrosis. Body mass index (OR = 1.08), serum lipid levels (OR = 0.96), viral load at diagnosis (OR = 1.00005), and low CD4+ cell count (OR = 0.977) were also correlated with liver fibrosis. The FIB-4 and APRI scores were strongly correlated with each other. In conclusion, HBV co-infection seems to be a determinant factor for liver fibrosis development in people living with HIV, together with other risk factors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

Abstract Atrial fibrillation (AF) is a prevalent cardiac arrhythmia, affecting millions worldwide and increasing in frequency with age. Despite progress in treatment and prevention, AF remains a significant contributor to stroke, heart failure, and overall cardiovascular morbidity. One particularly challenging type of AF, paroxysmal atrial fibrillation (PAF), is often asymptomatic, leading to delayed diagnosis and increasing the risk of severe complications like stroke. The advent of cardiac implantable electronic devices (CIEDs) has significantly improved the ability to detect subclinical AF or atrial high-rate episodes (AHRE), even in patients with no symptoms. These devices, particularly pacemakers, offer long-term, continuous monitoring of atrial rhythms, making them an invaluable tool for diagnosing AF early and assessing its burden in real time. This study focused on a cohort of patients from the Oltenia region who received dual-chamber pacemakers with no prior diagnosis of AF. The research aimed to monitor the incidence of AF in these patients over a follow-up period of 12 to 18 months and to identify potential clinical predictors for developing AF. A total of 91 patients were assessed in this study, all of whom received dual-chamber pacemakers by the pacing guidelines for conditions such as atrioventricular block and sick sinus syndrome. None of the patients had a history of AF at the time of implantation. Follow-up results indicated an incidence of AHRE in 13.19% of patients, with significant predictors including advanced age and the presence of hypertension. These findings align with the broader literature, which consistently associates both factors with an increased risk of AF. The study underscores the importance of continuous monitoring in pacemaker patients, particularly for detecting asymptomatic AF, which may necessitate specific therapeutic interventions. Although the study’s sample size was limited, its findings contribute valuable insights into managing AF in pacemaker patients, particularly regarding early detection and potential risk factors. Future research with larger cohorts is necessary to confirm and expand these results.

The outbreak of the coronavirus pandemic in March 2020 has caused unprecedented pressure on public health and healthcare. The spectrum of COVID-19 onset is large, from mild cases with minor symptoms to severe forms with multi-organ dysfunction and death. In COVID-19, multiple organ damage has been described, including lung damage, acute kidney injury, liver damage, stroke, cardiovascular and digestive tract disorders. The aspects of liver injury are different, sometimes presenting with only a slight increase in liver enzymes, but sometimes with severe liver injury, leading to acute liver failure requiring liver transplantation. In patients with chronic liver disease, especially liver cirrhosis, immune dysfunction can increase the risk of infection. Immune dysfunction has a multifactorial physiopathological mechanism, implying a complement system and macrophage activation, lymphocyte and neutrophil activity dysfunction, and intestinal dysbiosis. This review aims to evaluate the most relevant studies published in the last years related to the etiopathogenetic, biochemical, and histological aspects of liver injury in patients diagnosed with COVID-19. Liver damage is more evident in patients with underlying chronic liver disease, with a significantly higher risk of developing severe outcomes of COVID-19 and death. Systemic inflammation, coagulation disorders, endothelial damage, and immune dysfunction explain the pathogenic mechanisms involved in impaired liver function. Although various mechanisms of action of SARS-CoV-2 on the liver cell have been studied, the impact of the direct viral effect on hepatocytes is not yet established.

Irritable bowel syndrome (IBS) is a common digestive disorder with a significant impact on both individuals and society in terms of quality of life and healthcare costs. A growing body of research has identified various communication pathways between the microbiota and the brain in relation to motility disorders, with the gut–brain axis being key to the pathogenesis of IBS. Multiple factors contribute to the pathogenetic pathways in IBS, including immune mechanisms, psychosocial factors, increased oxidative stress and pro-inflammatory cytokine release, as well as genetic and hormonal factors. Increased permeability of the normal intestinal barrier allows bacterial products to access the lamina propria, providing a mechanism for perpetuating chronic inflammation and characteristic symptoms. The microbiota influences inflammatory processes in IBS by altering the balance between pro-inflammatory factors and host defence. Probiotics modulate the pathophysiological mechanisms involved in IBS by influencing the composition of the microbiota and improving intestinal motility disorders, visceral hypersensitivity, immune function of the intestinal epithelium, metabolic processes in the intestinal lumen, dysfunction of the microbiota-GBA, and are recognised as effective and safe in IBS therapy. Our study aimed to provide a comprehensive overview of the relationship between the gut–brain axis, microbiota, and IBS, based on current information.

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

The growing usage of glyphosate, dicamba, and 2,4-D herbicide mixtures to combat glyphosate-resistant weeds raises concerns about human health and environmental consequences. The purpose of this study was to see how developmental exposure to glyphosate and a herbicide mixture combining glyphosate, dicamba, and 2,4-D affected rat dams' liver structure and function. A mixture of glyphosate, dicamba, and 2,4-D each at their European Union acceptable daily intake (ADI) (0.5, 0.002, and 0.3 mg/kg bw/day, respectively) and glyphosate at the ADI and NOAEL levels (0.5 and 50 mg/kg bw/day), were administered to pregnant Wistar rats from day-6 of gestation until weaning. The dams were sacrificed after weaning, and blood and liver tissue collected. In dams, glyphosate exposure resulted in the induction of non-alcoholic liver disease in a dose-dependent manner. In addition, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL dose, suggesting at least an additive effect of the herbicide mixture at regulatory doses considered individually safe for humans.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40–50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.

Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis, and coagulation issues are the main causes of anemia. Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption. In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia. The use of interferon has been linked to bone marrow toxicity, and hemolytic anemia brought on by ribavirin is a well-known dose-dependent side effect. Within six months of the infection with hepatitis B, hepatitis C, and Epstein–Barr viruses, aplastic anemia associated with hepatitis is seen. This anemia is characterized by pancytopenia brought on by hypocellular bone marrow. Esophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia can all cause acute and chronic blood loss. These conditions can progress to iron deficiency anemia, microcytic anemia, and hypochromic anemia. Another common hematologic abnormality in liver cirrhosis is macrocytosis, with multifactorial causes. Vitamin B12 and folate deficiency are frequent in liver cirrhosis, especially of alcoholic etiology, due to increased intestinal permeability, dysbiosis, and malnutrition. Many chronic liver diseases, like viral and autoimmune hepatitis, have a chronic inflammatory substrate. Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia.

COVID-19 pneumonia represents a maximum medical challenge due to the virus's high contagiousness, morbidity, and mortality and the still limited possibilities of the health systems. The literature has primarily focused on the diagnosis, clinical-radiological aspects of COVID-19 pneumonia, and the most common possible differential diagnoses. Still, few studies have investigated the rare differential diagnoses of COVID-19 pneumonia or its overlap with other pre-existing lung pathologies. This article presents the main radiological features of COVID-19 pneumonia and the most common alternative diagnoses to establish the vital radiological criteria for a differential diagnosis between COVID-19 pneumonia and other lung pathologies with similar imaging appearance. The differential diagnosis of COVID-19 pneumonia is challenging because there may be standard radiologic features such as ground-glass opacities, crazy paving patterns, and consolidations. A multidisciplinary approach is crucial to define a correct final diagnosis, as an overlap of COVID-19 pneumonia with pre-existing lung diseases is often possible and suggests possible differential diagnoses. An optimal evaluation of HRTC can help limit the clinical evolution of the disease, promote therapy for patients and ensure an efficient allocation of human and economic resources.

A high risk of developing insulin resistance (IR) and, eventually, type 2 diabetes mellitus (T2DM) is associated with chronic hepatitis C virus (HCV). Multiple mechanisms can account for the development of IR in chronic HCV patients, steatosis or fatty liver that can lead to metabolic syndrome, and the inflammatory process associated with the presence of HCV infection. In this article, we analyze the reported values of homoeostasis model assessment (HOMA-IR) before and after successful direct-acting agents (DAAs) treatment in the literature (23 studies) at certain intervals, respectively 12, 24, and 52 weeks depending on the presence of T2DM among patients. The meta-analysis showed improvement of IR in most cases except for three studies that presented a minimal increase in HOMA-IR value for the non-T2DM group at the 12- and 24-week check-ups possibly hinting at a prediabetes group. All other studies showed an important decrease in HOMA-IR post-DAA treatment specifically for the T2DM group. The most significant change in HOMA-IR values was noticed after 24 weeks in all categories. Our meta-analysis showed that clearance of HCV leads to improvement of IR, especially in the case of patients with T2DM.

Diabetes Mellitus (DM) and Chronic Hepatitis C Virus (HCV) have a strong interconnection in general practice. Recent studies have correlated insulin resistance risk with liver dysfunction. Haptoglobin is a biomarker that is modified in liver disease and is involved in metabolic diseases. Our study aims to investigate the changes in haptoglobin and bilirubin levels after direct -acting antiviral (DAA) treatment for viral hepatitis C in relation to diabetes status and hypertension in order to identify potential biomarkers for the prognosis of liver disease in diabetic patients after obtaining sustained virological response (SVR). Eighty patients (40 with Type 2-DM (T2DM) and 40 without T2DM) treated with DAAs for HCV infection that obtained SVR were monitored for biochemical markers before and 3 years after treatment. We report that HCV clearance improves not only the biomarkers of liver function but also TB and Hp, which are strongly connected with insulin resistance in T2DM, leading to better control of blood glucose levels, obesity, and lipid metabolism. These two biomarkers should be further investigated not only to understand better the physiopathological pathways by which they affect TD2M progression, but also how their levels might be raised in the pursuit of better control of diabetes, cardiovascular complications, and other diseases.

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.

According to GLOBOCAN 2018 data Colorectal cancer (CRC) represents the third most commonly diagnosed cancer in the world and has the second-highest mortality rate. The incidence of CRC has been rising worldwide, the majority of cases being in developing countries mostly due to the adoption of an unhealthy lifestyle. The main driving factors behind CRC are a sedentary lifestyle, obesity, red meat consumption, alcohol, and tobacco; however, early detection screenings and standardized treatment options have reduced CRC mortality. Better family history and genetic testing can help those with a hereditary predisposition in taking preventative measures.

According to GLOBOCAN 2018 data Colorectal cancer (CRC) represents the third most commonly diagnosed cancer in the world and has the second-highest mortality rate. The incidence of CRC has been rising worldwide, the majority of cases being in developing countries mostly due to the adoption of an unhealthy lifestyle. The main driving factors behind CRC are a sedentary lifestyle, obesity, red meat consumption, alcohol, and tobacco; however, early detection screenings and standardized treatment options have reduced CRC mortality. Better family history and genetic testing can help those with a hereditary predisposition in taking preventative measures.

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age-related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse (TM)', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18-month-old rats. The administration of the 'Reverse (TM)' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR-ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse (TM)' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse (TM)' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle-aged rats through nutraceutical supplementation. The use of the 'Reverse (TM)' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Objective: Patients with chronic hepatitis C are subjected to a greater risk of cardiovascular disease and difficult to control diabetes mellitus type 2 (T2DM) comparatively to people that have never contracted Hepatitis C Virus (HCV). We aimed to investigate the impact of T2DM on HCV patients with the help of Fibromax test results compared to nonT2DM patients, and the metabolic differences between the 2 study groups. Our long term goals are to observe the long term impact of achieving systemic virusologic response (SVR) by means of Direct-Acting antivirals (DAA) between the 2 cohorts. Research Design and Methods: We selected a lot of 200 patients with HCV that will undergo interferon-free DAA-based antiviral treatment for HCV and we used the results of the Fibromax Test to compare the biological parameters of T2DM and nonT2DM patients. RESULTS Among patients with T2DM compared to NonT2DM there is a significant correlation on Steatotest, NashTest, GGT, Glycemia, body weight, height and BMI. Test also showed that 15,5% of the test group had elevated glycemia, indicating the probability of developing diabetes in the future. Conclusions: Our results suggest that HCV patients that also have T2DM are subjected to a combined higher risk of accelerated steatosis development, steatohepatitis, added difficulty in controlling glycemic levels. All these previous elements combined with a prevalence for patients to be overweight have a negative metabolic impact. Eradication of HCV with the help of DAA is important in order to help improving the metabolic impact of diabetes on steatosis, steatohepatitis. An added benefit is better management of glycemic control by decreasing insulin use and eliminating one risk factor of T2DM.