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Viruses May 2024: HCMV causes severe clinical complications in transplant recipients and may lead to graft rejection. Successful renal transplantation heavily relies on the early...
: HCMV causes severe clinical complications in transplant recipients and may lead to graft rejection. Successful renal transplantation heavily relies on the early prevention and diagnosis of CMV infections, followed by prompt prophylactic treatment before transplantation. Despite the majority of renal rejection cases with acute HCMV infections being asymptomatic and occurring one to two years later, the objective of this research was to comprehend the effect of late HCMV infection on renal rejection by examining specific clinical parameters in the Eastern Indian cohort. : In this study, 240 patients were studied for five years following transplantation, and their data were collected from the local metropolitan hospital in Eastern India. Both HCMV-positive and -negative post-transplant patients were investigated using the clinical parameters and viral loads for latent infection. : Within the studied population, 79 post-transplant patients were found to be HCMV positive. Among them, 13 (16.45%) patients suffered from renal rejection within less than 2 yrs. of transplantation (early rejection) and 22 (27.84%) patients suffered from renal rejection after 2 yrs. from the operation date (late rejection). Assessment of clinical parameters with respect to HCMV infection revealed that in early rejection cases, fever (-0.035) and urinary tract infection (-0.017) were prominent, but in late rejection, hematuria (-0.032), diabetes (-0.005), and creatinine level changes ( < 0.001) were significant along with urinary tract infection (-0.047). : This study provides valuable insights into monitoring latent CMV infections and highlights the understanding of reducing renal rejection rates and the need for further research in this field.
Topics: Humans; Cytomegalovirus Infections; Kidney Transplantation; India; Male; Female; Adult; Graft Rejection; Cytomegalovirus; Middle Aged; Viral Load; Cohort Studies; Young Adult; Transplant Recipients
PubMed: 38932140
DOI: 10.3390/v16060847 -
Viruses May 2024The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple... (Review)
Review
The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.
Topics: SARS-CoV-2; Humans; COVID-19; Animals; Spike Glycoprotein, Coronavirus; Mice; Post-Acute COVID-19 Syndrome; Angiotensin-Converting Enzyme 2; Peptides; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38932130
DOI: 10.3390/v16060838 -
Viruses May 2024The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent...
The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.
Topics: Animals; Mice; COVID-19; Disease Models, Animal; Murine hepatitis virus; SARS-CoV-2; Intestinal Mucosa; Intestines; Intestine, Small; Female
PubMed: 38932125
DOI: 10.3390/v16060832 -
Viruses May 2024HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be...
HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP ( 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.
Topics: Humans; Female; Male; Tanzania; Middle Aged; Risk Factors; HIV Infections; Aged; Prevalence; AIDS Dementia Complex; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Neurocognitive Disorders
PubMed: 38932112
DOI: 10.3390/v16060819 -
Pharmaceutics Jun 2024Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the...
Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the therapeutic application of silibinin is quite limited due to its poor bioavailability. In the present study, an attempt was made to improve the antidiabetic efficacy of silibinin by its encapsulation in liposomal vesicles. The liposomes with a high encapsulation efficiency of silibinin (96%) and a zeta potential of -26.2 ± 0.6 mV were developed and studied using nicotinamide/streptozotocin-induced diabetic rats. Administration of silibinin-loaded liposomes to diabetic rats lowered glucose levels, increased insulin levels, and improved pancreatic islet architecture. The anti-inflammatory effect of silibinin-loaded liposomes was demonstrated by a decrease in serum C-reactive protein (CRP) levels and a reduced deposition of collagen fibers in the islets of diabetic rats. Furthermore, silibinin-loaded liposomes were more efficient in lowering glucose, alanine transaminase, triglyceride, and creatinine levels in diabetic rats than pure silibinin. In addition, silibinin-loaded liposomes had a significantly better effect on beta-cell mass and Glut2 glucose receptor distribution in diabetic islets than pure silibinin. The present results clearly show that liposome encapsulation of silibinin enhances its antidiabetic efficacy, which may contribute to the therapeutic benefit of silibinin in the treatment of diabetes and its complications.
PubMed: 38931922
DOI: 10.3390/pharmaceutics16060801 -
Sensors (Basel, Switzerland) Jun 2024The precise segmentation of retinal vasculature is crucial for the early screening of various eye diseases, such as diabetic retinopathy and hypertensive retinopathy....
The precise segmentation of retinal vasculature is crucial for the early screening of various eye diseases, such as diabetic retinopathy and hypertensive retinopathy. Given the complex and variable overall structure of retinal vessels and their delicate, minute local features, the accurate extraction of fine vessels and edge pixels remains a technical challenge in the current research. To enhance the ability to extract thin vessels, this paper incorporates a pyramid channel attention module into a U-shaped network. This allows for more effective capture of information at different levels and increased attention to vessel-related channels, thereby improving model performance. Simultaneously, to prevent overfitting, this paper optimizes the standard convolutional block in the U-Net with the pre-activated residual discard convolution block, thus improving the model's generalization ability. The model is evaluated on three benchmark retinal datasets: DRIVE, CHASE_DB1, and STARE. Experimental results demonstrate that, compared to the baseline model, the proposed model achieves improvements in sensitivity (Sen) scores of 7.12%, 9.65%, and 5.36% on these three datasets, respectively, proving its strong ability to extract fine vessels.
Topics: Humans; Retinal Vessels; Neural Networks, Computer; Algorithms; Microvessels; Image Processing, Computer-Assisted; Diabetic Retinopathy; Retina
PubMed: 38931797
DOI: 10.3390/s24124014 -
Pharmaceuticals (Basel, Switzerland) Jun 2024(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At...
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot-cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.
PubMed: 38931450
DOI: 10.3390/ph17060783 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Millions of patients suffer from type 1 diabetes (T1D) and its associated complications. Nevertheless, the pursuit of a cure for T1D has encountered significant...
Novel Protein Biomarkers and Therapeutic Targets for Type 1 Diabetes and Its Complications: Insights from Summary-Data-Based Mendelian Randomization and Colocalization Analysis.
Millions of patients suffer from type 1 diabetes (T1D) and its associated complications. Nevertheless, the pursuit of a cure for T1D has encountered significant challenges, with a crucial impediment being the lack of biomarkers that can accurately predict the progression of T1D and reliable therapeutic targets for T1D. Hence, there is an urgent need to discover novel protein biomarkers and therapeutic targets, which holds promise for targeted therapy for T1D. In this study, we extracted summary-level data on 4907 plasma proteins from 35,559 Icelanders and 2923 plasma proteins from 54,219 UK participants as exposures. The genome-wide association study (GWAS) summary statistics on T1D and T1D with complications were obtained from the R9 release results from the FinnGen consortium. Summary-data-based Mendelian randomization (SMR) analysis was employed to evaluate the causal associations between the genetically predicted levels of plasma proteins and T1D-associated outcomes. Colocalization analysis was utilized to investigate the shared genetic variants between the exposure and outcome. Moreover, transcriptome analysis and a protein-protein interaction (PPI) network further illustrated the expression patterns of the identified protein targets and their interactions with the established targets of T1D. Finally, a Mendelian randomization phenome-wide association study evaluated the potential side effects of the identified core protein targets. In the primary SMR analysis, we identified 72 potential protein targets for T1D and its complications, and nine of them were considered crucial protein targets. Within the group were five risk targets and four protective targets. Backed by evidence from the colocalization analysis, the protein targets were classified into four tiers, with MANSC4, CTRB1, SIGLEC5 and MST1 being categorized as tier 1 targets. Delving into the DrugBank database, we retrieved 11 existing medications for T1D along with their therapeutic targets. The PPI network clarified the interactions among the identified potential protein targets and established ones. Finally, the Mendelian randomization phenome-wide association study corroborated MANSC4 as a reliable target capable of mitigating the risk of various forms of diabetes, and it revealed the absence of adverse effects linked to CTRB1, SIGLEC5 and MST1. This study unveiled many protein biomarkers and therapeutic targets for T1D and its complications. Such advancements hold great promise for the progression of drug development and targeted therapy for T1D.
PubMed: 38931433
DOI: 10.3390/ph17060766 -
Pharmaceuticals (Basel, Switzerland) Jun 2024() is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic...
() is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic and inflammatory diseases. is rich in mulinane- and azorellane-type diterpenoids. For two of these, acute hypoglycemic effects have been described, but the impact of diterpenoids on fatty liver disease has not been investigated. Therefore, organic fractions were prepared using petroleum ether, dichloromethane and methanol. Their content was characterized by UHPLC/MS, revealing the presence of ten diterpenoids, mainly mulinic acid, azorellanol and mulin-11,13-diene. Next, mice fed with a high-fat diet (HFD), a model of metabolic dysfunction-associated fatty liver disease (MAFLD), received one of the fractions in drinking water for two weeks. After this treatment, hepatic parameters were evaluated. The fractions did not reduce hyperglycemia or body weight in the HFD-fed mice but increased the serum levels of hepatic transaminases (AST and ALT), reduced albumin and increased bilirubin, indicating hepatic damage, while histopathological alterations such as steatosis, inflammation and necrosis generated by the HFD were, overall, not ameliorated by the fractions. These results suggest that organic extracts may generate hepatic complications in patients with MAFLD.
PubMed: 38931413
DOI: 10.3390/ph17060746 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in... (Review)
Review
Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium-glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.
PubMed: 38931402
DOI: 10.3390/ph17060736