Anticancer peptides (ACPs) are rising as a new strategy for cancer therapy. However, traditional laboratory screening to find and identify novel ACPs from hundreds to thousands of peptides is costly and time consuming. Here, a sequential procedure is applied to identify candidate ACPs from a computer-generated peptide library inspired by alpha-lactalbumin, a milk protein with known anticancer properties.
View Article and Find Full Text PDFCancer is the leading cause of death worldwide, resulting in the mortality of more than 10 million people in 2020, according to Global Cancer Statistics 2020. A potential cancer therapy involves targeting the DNA repair process by inhibiting PARP-1. In this study, classification models were constructed using a non-redundant set of 2018 PARP-1 inhibitors.
View Article and Find Full Text PDFThe inhibition of poly(ADP-ribose) polymerases (PARPs) and ataxia telangiectasia and Rad3-related (ATR) would be an alternative approach for cancer treatments. The aim of this study is to investigate the synergy of the different combinations of PARP inhibitors (olaparib, talazoparib, or veliparib) and ATR inhibitor AZD6738. A drug combinational synergy screen that combines olaparib, talazoparib, or veliparib with AZD6738 was performed to identify the synergistic interaction, and the combination index was calculated to verify synergy.
View Article and Find Full Text PDFRecent developments in chemotherapy focus on target-specific mechanisms, which occur only in cancer cells and minimize the effects on normal cells. DNA damage and repair pathways are a promising target in the treatment of cancer. In order to identify novel compounds targeting DNA repair pathways, two key proteins, 53BP1 and RAD54L, were tagged with fluorescent proteins as indicators for two major double strand break (DSB) repair pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR).
View Article and Find Full Text PDFTripartite motif-containing protein 29 (TRIM29) is involved in DNA double-strand break (DSB) repair. However, the specific roles of TRIM29 in DNA repair are not clearly understood. To investigate the involvement of TRIM29 in DNA DSB repair, we disrupted TRIM29 in DT40 cells by gene targeting with homologous recombination (HR).
View Article and Find Full Text PDFRing finger protein 43 (RNF43) is an E3 ubiquitin ligase which is well-known for its role in negative regulation of the Wnt-signaling pathway. However, the function in DNA double-strand break repairs has not been investigated. In this study, we used a lymphoblast cell line, DT40, and mouse embryonic fibroblast as cellular models to study DNA double-strand break (DSB) repairs.
View Article and Find Full Text PDFSpinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern.
View Article and Find Full Text PDFBackground: An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment.
View Article and Find Full Text PDFBackground: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis.
View Article and Find Full Text PDFAim: Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term.
View Article and Find Full Text PDFBackground And Objectives: Renal phosphate wasting occurs early postkidney transplantation as a result of an accumulation of parathyroid hormone and fibroblast growth factor 23 from the CKD period. Serum phosphate, parathyroid hormone, and fibroblast growth factor 23 return to baseline 1 year postkidney transplantation. What happens beyond this period is unknown.
View Article and Find Full Text PDFObjective: To evaluate 25 hydroxyvitamin D (25-OH-D) deficiency in a cohort ofpredialysis CKD patients and the treatment effect and safety of high dose ergocalciferol supplement in predialysis CKD.
Material And Method: Fifty-six predialysis CKD patients who came for a regular visit at a single hospital with calculated glomerular filtration rate < or =60 mL/min/1.73 m2 were screened for 25-OH-D levels.
Background: Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as endocrine function. Adipose tissue communicates with the rest of the body through synthesis and release adipokines, such as leptin, adiponectin and TNF-alpha. Adiponectin enhances insulin sensitivity and possesses anti-atherogenic and anti-inflammatory properties.
View Article and Find Full Text PDFObjective: To survey the urinary risk factors associated with recurrent calcium stone and the contribution of renal tubular acidosis to the prevalence of recurrent calcium stone formation in Thai recurrent stone formers.
Material And Method: There were 86 consecutive recurrent calcium stone formers. Three-day dietary record, serum biochemical parameters, first morning urine pH, and two 24-hour urine collections were obtainedfrom each subject.
Background: Multiple factors associated with hypocitraturia have been identified. However, limited studies addressing the causal relationship to hypocitraturia are available. We therefore conducted this study to determine factors associated with hypocitraturia and show their causal relationship in recurrent calcium stone formers.
View Article and Find Full Text PDFSoutheast Asian J Trop Med Public Health
December 2004
It has been speculated that calcium supplement in subjects with low oxalate intake might increase the risk of calcium stone formation due to an increase in calcium absorption without a significant reduction in oxalate absorption. There have been no human studies addressing specifically the effects of taking calcium supplements in populations whose dietary oxalate is low. This study was conducted to determine the effects of calcium supplements on the risk of calcium stone formation in a population with low oxalate intake.
View Article and Find Full Text PDFEnd-stage kidney disease has become an increasing burden in all regions of the world. However, limited epidemiologic data on chronic kidney disease in Southeast Asian populations are available. Therefore, a cohort study over a period of 12 yr (1985 to 1997) in 3499 employees of the Electric Generation Authority of Thailand, aged 35 to 55 yr, was conducted to determine the prevalence of decreased kidney function and risk factors associated with future development of decreased kidney function.
View Article and Find Full Text PDFBackground: 'Primary' osteoporosis has been associated with a high incidence of a renal acidification defect, incomplete renal tubular acidosis (iRTA). An acid loading test, to exclude the defect, has been recommended for inclusion in the work-up of osteoporosis. However, there is no community-based study to confirm its utility.
View Article and Find Full Text PDFOur previous report on bone histomorphometry in patients with distal renal tubular acidosis (dRTA) revealed decreased bone formation rate (BFR) when compared to healthy subjects. The abnormality improved significantly after alkaline therapy. The modest increase in osteoblastic surface, after correction of metabolic acidosis, could not explain the striking improvement in bone formation, suggesting additional influence of metabolic acidosis on osteoblast function and/or bone matrix mineralization.
View Article and Find Full Text PDFBackground: Variation in the timing of calcium supplement may affect gastrointestinal absorption of both calcium and oxalate differently and may associate with variable risk of calcium oxalate nephrolithiasis. There are few human studies addressing specifically the appropriate time for taking calcium supplement. Therefore, this study was performed to compare calcium bioavailability and the risk of calcium oxalate stone formation for calcium supplement taken with meal vs.
View Article and Find Full Text PDFUnlabelled: This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF-I was reduced and may modulate the reduction of bone mass.
Introduction: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited.
Cystine urinary stone is an autosomal recessive hereditary disease, frequently recurring and resisting fragmentation by Shockwave lithotripsy. As cases have never been reported before in Thailand, five cases of renal cystine stones at Ramathibodi Hospital were reported. Two were in the same family.
View Article and Find Full Text PDFBackground: Distal renal tubular acidosis (RTA) is a common cause of intractable calcium nephrolithiasis. In adults, the use of potassium citrate (PC) in distal RTA effectively decreases metabolic acidosis and the risk of calcium oxalate stone but it cannot decrease the risk of calcium phosphate stone. However, there is no report for the optimal dose of PC and the risk of calcium stone in distal RTA in children.
View Article and Find Full Text PDFBackground: The association between chronic metabolic acidosis and alterations in bone cell functions has been demonstrated in vitro and in animal studies. However, the causal role of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density and bone histology before and after correction of acidosis among patients with distal renal tubular acidosis (dRTA) METHODS: Correction of metabolic acidosis by potassium citrate was done in non-azotemic dRTA patients, 6 females and 4 males, who had never received long-term alkaline therapy before enrolling into this study.
View Article and Find Full Text PDFPotassium citrate is an alkaline agent that has been recommended for the prevention of nephrolithiasis in distal renal tubular acidosis (RTA). Information on the effectiveness and the optimal dose of potassium citrate in the correction of urinary abnormalities in pediatric distal RTA is limited, however. We conducted this study to determine the effectiveness and the optimal dose of potassium citrate for the correction of urinary abnormalities and the prevention of nephrolithiasis in children with distal RTA.
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