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Needle knife papillotomy for cannulating difficult papilla; two years experience.

INTRODUCTION: Osteoarticular TB contributes to roughly 10% of the cases of extrapulmonary TB. The incidence of osteoarticular tuberculosis is one of the lowest in extrapulmonary tuberculosis, probably only next to cutaneous tuberculosis in non-HIV patients. Considering the low incidence of primary osteoarticular tuberculosis without pulmonary tuberculosis, we hypothesise that there is an element of tissue-specific immunity against tuberculosis in the body, which appears to be very high in bone and joints. The concept of immunity against tuberculosis in general is well-established for pulmonary

Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss.

von Hippel-Lindau (VHL) is a critical tumor suppressor in clear cell renal cell carcinomas (ccRCCs). It is important to identify additional therapeutic targets in ccRCC downstream of VHL loss besides hypoxia-inducible factor 2α (HIF2α). By performing a genome-wide screen, we identified Scm-like with four malignant brain tumor domains 1 (SFMBT1) as a candidate pVHL target. SFMBT1 was considered to be a transcriptional repressor but its role in cancer remains unclear. ccRCC patients with VHL loss-of-function mutations displayed elevated SFMBT1 protein levels. SFMBT1 hydroxylation on Proline resi

The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta.

Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen, and CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1, and SP7 mutations were recently detected in a minority of patients with autosomal recessive OI. However, these findings have been mostly restricted to Western populations. The proportion of mutations and the correlations between genotype and phenotype in Chinese patients with OI are completely unknown. In this study, mutation analyses were performed for COL1A1, COL1A2, CRTAP, and LEPRE1 in a cohort of 58 unrelated Chi

Genetic and Clinical Spectrum of Osteogenesis Imperfecta in an Egyptian Cohort With a High Rate of Lethal Phenotypes.

Osteogenesis imperfecta (OI) is a genetically heterogeneous connective tissue disorder marked by bone fragility and deformities. This study aimed to define the clinical and molecular characteristics of 21 OI patients from 15 unrelated Egyptian families. Most probands were analyzed by exome sequencing. In three consanguineous cases, variants were identified through SNP array-based homozygosity mapping followed by direct sequencing of a candidate gene. Genotype-phenotype correlations were additionally explored. Parental consanguinity was documented in 66.7% (10/15) of the total cohort and in 100

Clinical and molecular analysis in families with autosomal recessive osteogenesis imperfecta identifies mutations in five genes and suggests genotype-phenotype correlations.

Autosomal recessive osteogenesis imperfecta (AR-OI) is an inherited condition which in recent years has been shown with increasing genetic and clinical heterogeneity. In this article, we performed clinical assessment and sought mutations in patients from 10 unrelated families with AR-OI, one of whom was presented with the additional features of Bruck syndrome (BS). Pathogenic changes were identified in five different genes: three families had mutations in FKBP10, three in SERPINF1, two in LEPRE1, one in CRTAP, and one in PPIB. With the exception of a FKBP10 mutation in the BS case, all changes

Activation of the hypoxia-inducible factor pathway by roxadustat improves glucose metabolism in human primary myotubes from men.

AIMS/HYPOTHESIS: Hypoxia-inducible factor prolyl 4-hydroxylase (HIF-P4H) enzymes regulate adaptive cellular responses to low oxygen concentrations. Inhibition of HIF-P4Hs leads to stabilisation of hypoxia-inducible factors (HIFs) and activation of the HIF pathway affecting multiple biological processes to rescue cells from hypoxia. As evidence from animal models suggests that HIF-P4H inhibitors could be used to treat metabolic disorders associated with insulin resistance, we examined whether roxadustat, an HIF-P4H inhibitor approved for the treatment of renal anaemia, would have an effect on g

Study on HIF-PHI combined with iron supplement in treatment of renal anemia in rats.

BACKGROUND: Roxadustat is a novel hypoxia- inducible factor-prolyl hydroxylase inhibitor(HIF-PHI) used to treat anemia in chronic kidney disease (CKD) patients. It has been reported that roxadustat can slow down kidney damage and delay the development of kidney fibrosis. Anemia and iron deficiency are often associated with the vast majority CKD patients, and insufficient available iron or total iron storage is often the most common cause of anemia and ESAs resistance in CKD patients. The role of iron availability in the pathogenesis of anemia in chronic kidney disease has received increasing a

Vadadustat Three Times Weekly in Patients With Anemia Due to Dialysis-Dependent CKD.

RATIONALE & OBJECTIVE: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) may offer an alternative to erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in the setting of chronic kidney disease (CKD). The objective of this study was to investigate the efficacy and safety of conversion from the long-acting ESA methoxy polyethylene glycol-epoetin-ß (MPG-EPO) to the oral HIF-PHI vadadustat 3 times weekly versus maintenance therapy with MPG-EPO. STUDY DESIGN: Phase 3b, open-label, noninferiority trial. SETTING & PARTICIPANTS: Multicenter study in the United State

[Mechanism of total flavonoids from Smilacis Glabrae Rhizoma against obesity-associated colorectal cancer via regulation of fatty acid oxidation].

This study aimed to investigate the mechanism of total flavonoids from Smilacis Glabrae Rhizoma(SGF) against obesity-associated colorectal cancer(CRC) via regulation of fatty acid oxidation(FAO). In vivo, syngeneic subcutaneous and orthotopic xenograft models of CRC cells MC38 were established in obese mice induced by high fat diet(HFD), which was followed by the administration with SGF. The tumor volume and tumor weight were measured in the CRC subcutaneous model. The growth of CRC orthotopic tumors was monitored by a small animal in vivo imaging system. Hematoxylin-eosin(HE) staining was use

Copper metabolism in cell death and autophagy.

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and the function of transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, and cuproptosis. Furthermore, copper ions can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays a dual role in regulating the survival or death fate of cells under various stress conditions. Pathologically, impaired copper metabolism due to environmental or genetic

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.

BackgroundRoxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear.Methods/designThis is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annua

Comparison of efficacy of roxadustat and erythropoietin for the treatment of renal anemia in patients with chronic kidney disease: a retrospective study.

BackgroundRenal anemia is a common complication in patients with end-stage renal disease (ESRD). Both roxadustat and recombinant human erythropoietin (rhEPO) are alternative option for patients with renal anemia. However, the adverse events of rhEPO limited the wide use of it and the concrete difference of real clinical efficacy of rhEPO and roxadustat was still uncertain. This study aimed to assess the clinical efficacy of roxadustat for improving renal anemia in patients with chronic kidney disease.MethodsA retrospective cohort study of 790 consecutive patients with renal anemia treated with

Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.

Ascorbic acid has attracted substantial attention for its potential antitumor effects by acting as an antioxidant in vivo and as a cofactor in diverse enzymatic reactions. However, solid proof of its clinical efficacy against cancer and the mechanism behind its effect have not been established. Moreover, cancer forms cancer-specific microenvironments and interacts with various cells, such as cancer-associated fibroblasts (CAFs), to maintain cancer growth and progression; however, the effect of ascorbic acid on the cancer microenvironment is unclear. This review discusses the effects and mechan

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… | Collagen prolyl hydroxylases (C-P4H) | Proline hydroxylases | Factor inhibiting HIF-1 | DNA/histone demethylases (TETs/JHDMs) Effect | Promotes collagen production by stabilizing the three-dimensional structure of procollagen through hydroxylation of its proline. | Degrade HIFα via ubiquitination … Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor . Proc Natl Acad Sci USA ( 2002 ) 99 : 13459–64 . doi: 10.1073/pnas.192342099 PMC129695 12351678 41 Hewitson KS McNeill LA Riordan MV Tian YM Bullock AN Welford RW . …

Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much highe

Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.

There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF-κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating an

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

Anemia of Chronic Diseases: Wider Diagnostics-Better Treatment?

Anemia of chronic diseases is a condition that accompanies a specific underlying disease, in which there is a decrease in hemoglobin, hematocrit and erythrocyte counts due to a complex process, usually initiated by cellular immunity mechanisms and pro-inflammatory cytokines and hepcidin. This is the second most common type of anemia after iron deficiency anemia in the world. Its severity generally correlates with the severity of the underlying disease. This disease most often coexists with chronic inflammation, autoimmune diseases, cancer, and kidney failure. Before starting treatment, one sho

Risk factors and current state of therapy for anemia after kidney transplantation.

Post-transplant anemia is one of the most common complications in kidney transplant recipients, severely affecting patient prognosis and quality of life, and is an independent predictor of graft kidney loss and patient mortality. However, our clinical understanding and the attention given to post-transplant anemia are currently insufficient. This paper reviews the current status, risk factors, and therapeutic progress in anemia after transplantation in kidney transplant recipients. We recommend that clinical staff pay attention to anemia and its complications in kidney transplant recipients an

Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis.

Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone m

Experimental Drugs for Chemotherapy- and Cancer-Related Anemia.

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Stan