Mechanisms underlying the antihypertensive effects of garlic bioactives

Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease–associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor–κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management.     

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.     

CRT in a congenital heart disease patient with interventricular dyssynchrony due to an RV conduction delay

We encountered a unique pattern of cardiac dyssynchrony in a patient with complex congenital heart disease (heterotaxy syndrome) with a biventricular physiology and systemic left ventricle (LV). On speckle tracking echocardiography, dyssynchrony was not detected within the LV, but was noted in an interventricular fashion between the LV and right ventricle (RV). An electrophysiologic study revealed a conduction delay in the subpulmonary RV. Cardiac resynchronization therapy provided reverse cardiac remodeling and an excellent result in our patient by placing the pacing leads around the dyssynchronous lesion.     

Surgically treated ovarian endometriosis association with BRCA1 and BRCA2 mutations

Endometriosis is associated with an increased risk of ovarian cancer. Few studies have also shown increased risk of breast cancer. BRCA1/2 mutations are linked to an increased risk of breast and ovarian cancers but their relation to endometriosis is unknown.     

Experience of decortication for restrictive hemodynamics in adults with congenital heart disease

We treated four postoperative adults with congenital heart disease with severe restrictive hemodynamics (RH), and performed decortication (DC) with the anticipation of some relief of the RH. The catheterizations before DC showed high central venous, and right and left ventricular end‐diastolic pressures with “dip‐and‐plateau” pressure waveforms in the right and left ventricles. Upon myocardial histopathologic examination, moderate myocardial fibrotic change was demonstrated in two of three cases. DC led to decrease in type B natriuretic peptide levels in all cases, resulting in a decline in the central venous, right and left ventricular end‐diastolic pressures in three cases. Successful DC‐related relief of RH, dilatation of the ventricles with decline in central and end‐diastolic pressures, was observed in only one case. Our limited DC‐related hemodynamic improvement indicates a complexity of the severe RH, which may represent a unique intractable heart failure pathophysiology in intractable postoperative adult congenital heart disease.     

Metastatic Tumors to the Gingiva and the Presence of Teeth as a Contributing Factor: A Literature Analysis

Background: Gingiva that is prone to inflammation may serve as a pre‐metastatic niche for the attraction of circulating malignant cells. The aim of this study is to analyze cases of metastatic lesions to the gingiva compared with cases metastasizing to other oral mucosal sites. The pathogenesis of gingival metastases is discussed, with emphasis on the role of inflammation. Methods: The English‐language literature between 1916 and 2011 was searched for cases of metastatic lesions to the oral mucosa; only cases metastasizing in the oral mucosa, gingiva, and periodontium were included. Results: Two hundred seven cases were included. The gingiva was the most common site (60.4%), followed by tongue and tonsil. The most common primary sites were lung (24.2%), kidney (13.5%), skin (10.6%), and breast (8.7%). In 27%, the oral lesion was the first sign of a malignant disease. In most cases, the lesion appeared as an exophytic mass (96%) diagnosed clinically as a reactive gingival lesion. The presence of teeth was significantly associated with the development of gingival metastases: in 108 of 125 gingival metastases, the lesion was found adjacent to teeth (P <0.001; odds ratio = 8.2). The average life expectancy after diagnosis of the metastasis was 3.7 months. Conclusions: The gingiva is the most common site for metastases to oral soft tissues, with strong association with the presence of teeth. This finding may be related to the role of inflammation in the attraction of metastatic cells to chronically inflamed gingiva.     

Impact of the COVID-19 Pandemic on Glycemic Control and Blood Pressure Control in Patients with Diabetes in Japan

Objective In this study, we investigated whether and how the COVID-19 pandemic affected glycemic control and blood pressure (BP) control in patients with diabetes mellitus (DM). Methods DM patients whose HbA1c level was measured regularly before and after the declaration of a state of emergency were included in this study. Some patients were given questionnaires about changes in their lifestyle to determine the factors affecting glycemic control and BP control. Results The median HbA1c level of the 804 patients increased significantly from 6.8% before the state of emergency to 7.1% and 7.0% during and after the state of emergency, respectively. This was in contrast to the decrease one year earlier due to seasonal variations. In the 176 patients who responded to the questionnaire, the HbA1c level also increased significantly during and after the state of emergency. The worsening of glycemic control was more pronounced in the group that had achieved HbA1c of <7% before the state of emergency than in those with higher values. Unlike the rise in HbA1c, the BP did not rise during the state of emergency but did rise significantly afterwards. There was no marked decrease in HbA1c or BP after the state of emergency, even in patients who responded that they were much more careful with their diet, ate less, or exercised more. Conclusions The COVID-19 pandemic worsened glycemic control and BP control, even in patients who perceived no marked change in their diet or exercise, suggesting that more active lifestyle guidance is necessary for good treatment of DM patients.     

Lactoferrin Prevents Hepatic Injury and Fibrosis via the Inhibition of NF-κB Signaling in a Rat Non-Alcoholic Steatohepatitis Model

Non-alcoholic steatohepatitis (NASH) can cause liver cirrhosis and hepatocellular carcinoma (HCC), with cases increasing worldwide. To reduce the incidence of liver cirrhosis and HCC, NASH is targeted for the development of treatments, along with viral hepatitis and alcoholic hepatitis. Lactoferrin (LF) has antioxidant, anti-cancer, and anti-inflammatory activities. However, whether LF affects NASH and fibrosis remains unelucidated. We aimed to clarify the chemopreventive effect of LF on NASH progression. We used a NASH model with metabolic syndrome established using connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rats. Cx32ΔTg rats (7 weeks old) were fed a high-fat diet and intraperitoneally injected with dimethylnitrosamine (DMN). Rats were divided into three groups for LF treatment at 0, 100, or 500 mg/kg/day for 17 weeks. Lactoferrin significantly protected steatosis and lobular inflammation in Cx32ΔTg rat livers and attenuated bridging fibrosis or liver cirrhosis induced by DMN. By quantitative RT–PCR, LF significantly down-regulated inflammatory (Tnf-α, Il-6, Il-18, and Il-1β) and fibrosis-related (Tgf-β1, Timp2, and Col1a1) cytokine mRNAs. Phosphorylated nuclear factor (NF)-κB protein decreased in response to LF, while phosphorylated JNK protein was unaffected. These results indicate that LF might act as a chemopreventive agent to prevent hepatic injury, inflammation, and fibrosis in NASH via NF-κB inactivation.