Abstract: A subset of renal tumors (5-8%) are associated with syndromes such as von Hippel-Lindau (VHL) syndrome, Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), and BRCA1 associated protein (BAP1) tumor predisposition syndrome, succinate dehydrogenase RCC (SDHB/C/D). These syndromes have their specific defined genetic alterations and associated extrarenal manifestations. Due to varying histopathology and aggressiveness of the tumors amongst these syndromes, the management strategies can range from active surveillance to upfront surgical resection. This review delineates specific characteristics of the most common familial renal cancer syndromes and discusses current management strategies. ... Read more

Abstract: Based on the abundant published literature, here we expand the understanding of cardiovascular diseases in a framework already presented in previous articles. In this context, some unique distinguishing features of vascular lesions are explained. A rationale for the role of apolipoprotein apoB100 is presented. It is hypothesized that K_ATP channels and their control by blood pH are behind the development of coronary artery spasm and cardiomyocyte death. Finally, the main cardiovascular risks are explained within the proposed framework. ... Read more

Abstract: Population-based estimates of the differences -in metastatic pattern, incidence, and prognosis of breast cancer patients by histologic grade at breast cancer diagnosis are lacking. Patients with breast cancer and metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic and Cox regression were performed to determine the effect of histologic grade on the presence of metastases at diagnosis and all-cause mortality. We identified a population-based sample of adult patients diagnosed with invasive breast cancer between 2010 and 2015 for whom the presence or absence of metastases was known. We depicted the landscape of metastatic pattern of breast cancer histologic grade that the percentage of bone metastasis was decreasing with higher histologic grade, while the percentages of lung and brain metastasis were increasing. Higher histologic grade was associated with a greater incidence of all metastatic lesions. Median durations of survival with distant metastasis were 41 months (Grade I), 34 months (Grade II), 21 months (Grade III), 13 months (Grade IV), and 16 months (unknown histologic grade). Grade III and unknown histologic grade represent the most common part of patients with metastatic disease, but not for breast cancer patients without metastasis. In multivariate analysis, Grade II, III, IV, and unknown histologic grade were associated with significantly greater odds of patients with metastatic disease to any distant site, compared with Grade I, but not to bone. Grade III was associated with increased all-cause mortality among patients having metastases to any sites, bone, brain, liver, and lung compared with Grade I, but not Grade II and Grade IV. Breast cancer histologic grades are associated with distinct patterns of metastatic spread and notable differences in survival. ... Read more

Abstract: COVID-19 infection can cause damage to various systems, such as cardiovascular, respiratory, and neurological, both during the course of the disease and in the period after recovery, caused by the effects of so-called "Long COVID." Cardiovascular complications caused by COVID-19 infection are not yet fully understood and characterized. Cardiovascular complications caused by COVID-19 include pericarditis, myocarditis, dysrhythmias, ischemic and non-ischemic heart disease, and thromboembolic disease. The pathophysiological and molecular mechanisms of cardiovascular damage caused by SARS-CoV-2 are still being studied. More severe COVID-19 cases with the multisystem inflammatory syndrome (MIS) have frequent involvement of cardiovascular damage. In addition, recent evidence shows that months later, individuals who have had a COVID-19 infection may be at a greater risk of suffering heart disease than individuals who have not had the infection. In this brief literature review, we summarize the current evidence in the literature on cardiovascular damage caused by COVID-19, during the period of infection and in the long COVID, and possible concomitant risk factors, which may play an important role. ... Read more

Abstract: Background: Studies have suggested that age and the serum total cholesterol (TC) concentration are independent risk factors for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH); however, the relationship between age and TC in patients with FH is unclear. We aimed to investigate the correlation between age and TC in patients with FH. Methods: In this study, 103 patients with FH and 106 non-FH controls were recruited from 2004 to 2017. Spearman and partial correlation analyses, as well as multiple regression analyses, were used to evaluate the relationship between TC and age. Results: There were no significant differences in age, gender, or BMI between the FH group and the control group (p > 0.05). Family history of CVD, TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) (Lp[a]), and non-HDL-C levels were significantly higher in patients with FH compared with the controls (p < 0.01). Additionally, the serum TC levels for ages ≥ 50 years were significantly higher than those for ages < 50 years (p < 0.05) in FH patients. In both Spearman and partial correlation analyses, age was found to be significantly correlated with serum TC (p < 0.001) in the FH group but not in the control group, which was confirmed by further multiple linear regression analyses and logistic regression analyses. Conclusions: Age is an independent factor influencing serum TC level in patients with FH, and it is necessary to conduct early screening and early intervention. ... Read more

Abstract: Pernicious anemia (PA) is an autoimmune disease characterized by cobalamin deficiency (CD) due to immune-mediated chronic atrophic gastritis (CAG). CD results from poor absorption of dietary cobalamin from the terminal ileum, triggered by positive intrinsic factor (IF) antibodies. It is the most common cause of CD worldwide. Despite advances in understanding biochemistry and pathogenesis of PA, its diagnosis can be extremely challenging as the disease may present with hematological as well as nonhematological manifestations and also because of unreliable serum cobalamin assays. Nonhematological manifestations may present in a patient with PA even in the absence of hematological findings. Herein, an overview of common and uncommon nonhematological manifestations of PA is discussed. ... Read more

Abstract: Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), has a mortality rate that is among the highest. The single therapy option that has the potential to be curative for the illness is surgery, which is generally accepted as being the only effective treatment available. This is because most pancreatic tumors are intractable to chemotherapy. Because of the severe nature of the illness that these tumors cause, only around twenty percent of these tumors can be surgically removed when the first symptoms appear. This is due to the harm that these tumors cause. Since surgery in late-stage cases does not usually offer benefits, here we shed light on the molecular mechanisms of the most aggressive pancreatic tumors that are highly resistant to drugs. We also describe two latest novel treatment approaches that are used to combat this fierce tumor: targeting exosome-mediated tumor-enhancement mechanisms and radiation therapy in combination with adverse effect-mitigating agents. Effective treatments for pancreatic cancer are needed to meet this urgent medical need. ... Read more

Abstract: Neurodegeneration is an increasing problem of aging. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are the most frequent forms of age-related neurodegeneration. Infectious diseases, in general, confer a risk of AD. Influenza and pneumonia vaccinations reduce risk of AD. Being vaccinated against pneumonia between ages 65-75 is associated with a reduction in the risk of AD afterwards. Protection against bacterial and viral infection is beneficial to the brain since these infections may activate dormant herpes simplex type 1 (HSV-1) and herpes zoster virus (HZV). HSV-1 and HZV may interact to trigger AD. Shingles (HZV) vaccine Zostavax reduces risk of AD and PD. This finding is consistent with the link between viruses and neurodegeneration. Herpes virus-induced reactivation of embryologic pathways silenced at birth could be one of the pathologic processes in AD and PD. Once embryologic reactivation has occurred in the brain of an older person and AD or PD develops, this complex process relentlessly destroys the protective mechanism it created in utero. Unanswered question: Are the AD-risk-reducing effects of flu, pneumonia, and shingles vaccinations cumulative? ... Read more

Abstract: Poly (ADP-ribose) polymerase 1 (PARP1) plays an irreplaceablerole in the progression of diabetic retinopathy (DR). The m6A methylation in mRNA controls gene expression under various physiological and pathological conditions. However, effects of m6A methylation on PARP1 expression and DR progression at molecular level have not been documented. This study shows that the levels of PARP1, inflammatory factors, and fibrosis markers were significantly upregulated via evaluation by real-time PCR, western blotting, and immunofluorescence in both in vivo and in vitro experiments. EdU, CCK8, and apoptosis assays demonstrate that knockdown of PARP1 not only significantly improved the vitality of hRMECs (human retinal microvascular endothelial cells) even under high glucose conditions but also prevented glucose-induced inflammation, fibrosis, and angiogenesis in vivo. Mechanistically, dot blot, RNA pull-down, and immunoblots were implemented to explore the mechanism of m6A-mediated PARP1 stability and function. PARP1 is identified as a target of YTHDF2-mediated m6A modification. Overexpression of YTHDF2 substantially suppressed PARP1 mRNA m6A modification and inhibited its mRNA expression. Collectively, it has been demonstrated that PARP1 is frequently upregulated in human retinas and contributes to DR progression, and that YTHDF2-mediated m6A modification epigenetically regulates diabetes-induced PARP1 expression. Findings from this work may engender therapeutic targets for treating diabetic retinopathy. ... Read more

Abstract: Sepsis is a life-threatening organ dysfunction caused by the maladjustment of the body's response to infection. Abnormal immune response plays an important role in the progression of sepsis, and immunomodulatory therapy is a promising therapeutic strategy for sepsis. Great efforts have been made recently to elucidate the mechanism by which immune dysfunction contributes to sepsis, and identify potential biomarkers and targets for the diagnosis and therapy of sepsis induced by emerging pathogens, especially for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. In this review, we summarize recent progress on the understanding of immune dysregulation involved in sepsis, and highlight potential biomarkers and targets to evaluate immune status of the patients with sepsis for individualized and precise immunotherapy. ... Read more