The metabolic syndrome: what to treat, how to treat, what are the goals?

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that include obesity, atherogenic dyslipidemia, raised blood pressure, and insulin resistance. The growing trend of obesity is associated with increased prevalence of metabolic syndrome. Optimizing diet and exercise are still the leading therapy for controlling the metabolic syndrome. Based on the current evidence, further emphasis should be placed on aggressive management of other metabolic risk factors such as high blood pressure and dyslipidemia.     

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non–small-cell lung cancer (NSCLC) with uniformly ¹³C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in ¹³C₆-glucose or ¹³C₅,¹⁵N₂-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation.     

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26–38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.     

The Effect of Alloplastic Bone Graft and Absorbable Gelatin Sponge in Prevention of Periodontal Defects on the Distal Aspect of Mandibular Second Molars,After Surgical Removal of Impacted Mandibular Third Molar: A Comparative Prospective Study

Aim

Recent studies claim that haemostatic agents can be used as bone graft substitutes. The aim of this study was to compare the efficacy of alloplastic bone graft with absorbable gelatin sponge in prevention of periodontal defects distal to mandibular second molar after the surgical removal of impacted mandibular third molars.

Materials and methods

A prospective, randomized, single-blind split-mouth study was designed. The study consisted of 25 patients requiring surgical removal of bilateral impacted mandibular 3rd molars. The surgical sites were randomly divided into 2 groups: group I: G-graft (hydroxyapatite + collagen, study group) and group II: Abgel (absorbable gelatin sponge, control group). Patients were recalled on lst and 7th postoperative days and 3rd and 6th postoperative months. Probing depth, alveolar bone levels and soft tissue wound healing were evaluated. Paired t test was used to compare pre and post-operative alveolar bone levels and probing depth (PD). Wilcoxon signed ranks test was used to compare the wound healing.

Results

The soft tissue wound healing, PD and the distance between the cemento–enamel junction on the distal aspect of mandibular second molar (point A) and the alveolar crest on the distal aspect of the same tooth (point B) were significantly higher in group I as compared to group II.

Conclusion

This study reveals an increase in the alveolar bone level, improvement of PD and better wound healing in group I. Group II subjects required longer healing time than the normal. The authors disagree the claim that the haemostatic agents can be used as bone graft substitutes. However, long-term, multicenter, randomized controlled clinical trials are required.     

Alcoholic Liver Disease and COVID-19 Pneumonia: A Case Series

The novel coronavirus 2019 (COVID-19) was reported by the World Health Organization in December 2019, and since then it has progressed into a worldwide pandemic, causing significant morbidity and mortality. Gastrointestinal symptoms of COVID-19 and elevated liver chemistries are seen in up to 50% of infected patients. Recent reports have suggested a high mortality rate for COVID-19 in patients with pre-existing liver disease, having an associated mortality of 39.8%. Alcoholic liver disease is a significant cause of morbidity and mortality in New Mexico (USA), and we report here the clinical course and characteristics of three cases of patients with alcoholic cirrhosis who were admitted to our hospital with COVID-19.