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Summary The study aimed to screen mutation of human homeostatic iron regulator (HFE) in colorectal carcinoma (CRC) and detect their associations with clinicopathological parameters. Expression of HFE was determined by quantitative polymerase chain reaction in matched CRC and non neoplastic colorectal mucosal tissue of 76 patients. Genomic DNA extracted were subjected to high high-resolution melt curve analysis and Sanger sequencing to detect mutations in HFE. The associations of the identified mutations with a variety of clinical features were determined. Approximately 60% of CRC showed low HFE expression. Of the ten 10 mutations identified in exons 2 and 4, c.187C>G (H63D), c845G>A (C282Y), c.193A>T (S65C), g.3828T>C, g.5795T>C, and g.5728G>A were known mutations. Four novel mutations were discovered; : c.184G>A, c.220T>G, c.322A>C, and c.324T>C. Heterozygous H63D and C282Y mutations were seen in 71% and 49% of cancer tissue, respectively. Tumour site (p = 0.048) and gender (p = 0.039) were significantly associated with H63D and C282Y mutation status, respectively. Local spread of cancer was significantly associated with C282Y mutations in CRC cancer and adjacent non-neoplastic tissue (p = 0.029 & and p = 0.004, respectively). There was a statistically significant association between H63D and C282Y negativity in matched non-neoplastic colorectal mucosa tissue and pathological staging of cancer (p = 0.047 & and p = 0.001, respectively). Patients with H63D and C282Y mutations in cancer tissue tend to have higher survival rates. Hence HFE mutations are common in CRC and are associated with clinicopathological parameters, implying the potential clinical significance of HFE mutations in colorectal carcinogenesis.

Chemical stability is a critical issue and prerequisite for realizing intended engineering applications of materials and is closely correlated to practical implementation efficiency, operation cost, and environmental impact. Herein, we demonstrate that the intrinsic characters of graphitic carbon nitride (CN)-based photocatalysts lead to a varying degree of photoinduced decomposition of CN. Elevated photochemical instability was shown as a synergistic consequence of a downshifting of the valence band potential and an enlarged surface area in CN. CN self-decomposition pathways involving superoxide (O2•‒) radicals and holes (h+) have been explored. A greater deterioration in the photocatalytic degradation efficiency of the target pollutant, diclofenac (DCF), was found in CN samples with inferior photostability, wherein sp2 C–N C nitrogen atoms in CN deteriorated during usage. Additionally, the presence of aromatic-rich humic acid slows down both the photoinduced self-decomposition of CN and the degradation of DCF by CN. The compiled results identified factors affecting the photodurability of CN, which inform a guiding framework for advancing the material design of CN-based materials toward boosting its long-term catalytic performance in water treatment, and the need of considering stability in the ongoing effort of improving CN’s photocatalytic efficiency is highlighted.

Immunohistochemistry (IHC) is an economic and precise method to localize the presence of specific protein at cellular level in tissue. Although many papillary thyroid carcinomas do not require IHC to render a diagnosis, there are certain scenarios in which IHC are important. The major diagnostic applications of IHC include confirmation of papillary thyroid carcinoma in sites other than the thyroid, distinguish papillary thyroid carcinoma from other primary thyroid neoplasms in thyroid, and identify papillary thyroid carcinoma from secondary tumors to the thyroid. At research level, IHC could help identify prognostic information, identify underlying genetic alterations, and predict response to treatment in papillary thyroid carcinoma. The understanding of principle and recent advances in IHC will improve the diagnosis and management of patients with thyroid lesions including papillary thyroid carcinoma.

A metal-free heterostructure system composed of graphitic carbon nitride (g-C3N4), reduced graphene oxide (rGO), and cyclooctasulfur (α-S) is developed as a facile route for establishing efficient photocatalysts. We aim to identify the governing factors that contributed to the photochemical performance of g-C3N4/rGO/α-S nanocomposites, which are important to advance potential applications but remain unexplored. The results indicate that the constituent ratio of each component in g-C3N4/rGO/α-S composites leads to varying surface microstructure, band alignment, and photochemical properties. The enhanced visible-light photocatalytic activity originates from an upward shift of the conduction bands toward higher energies, higher content of sp2-hybridized pyridine nitrogen in triazine rings (C N–C), and a lower amount of hydrogen bonds. The established structural integration informs a guiding framework for the design of emerging g–C3N4–based nanocomposites. Additionally, the influence of humic acid (HA) on photocatalytic decontamination was studied and shows an overall detrimental effect on the photocatalytic activity of g-C3N4 nanocomposites. Although HA advanced the photoexcited electrons, and therefore the reactive oxygen species, as well as enhanced the adsorption of the pollutants onto g-C3N4, especially at lower pH, attenuation of oxygen transfer as a result of active site competition between oxygen and target pollutants was found.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical investigations of AF in patients with DM have been scant and inconclusive. This article provides a comprehensive review of research findings on the association between DM and AF and critically analyzes the effect of different pharmacological classes of antidiabetic drugs on AF.

The sex and age differences in the relationship between vitamin D and lipid levels remain unclear. This retrospective study investigated the correlations between serum 25-hydroxyvitamin D levels and various biomarkers, along with the sex and age differences in these associations, among 573 men and 436 women during physical check-ups. The mean age of the study population was 51.4 years, and 66% of people had serum 25(OH)D levels below 30 ng/mL. People aged over 65 years had higher 25(OH)D levels than those younger than 65 years, and women had lower 25(OH)D levels than men. Younger age (odds ratio (OR) per year = 1.044, 95% CI, 1.029–1.059, p < 0.0001), female sex (OR = 1.779, 95% CI, 1.149–2.755, p = 0.0097), and elevated serum triglyceride (TG) levels (OR per 1 mg/dL = 1.005, 95% CI, 1.002–1.007, p = 0.0002) were all independent risk factors for vitamin D deficiency. Serum 25(OH)D levels were inversely associated with TG levels. The positive association between vitamin D deficiency and hypertriglyceridemia was significant in men (not in women) and in those aged between 50 and 65 years. In conclusion, younger individuals, women, and middle-aged men with hypertriglyceridemia are at higher risk of vitamin D deficiency.

Galectin-3 (Gal-3) is a biomarker of atrial fibrillation (AF) that mediates atrial inflammation. CD98 is the membrane surface receptor for Gal-3. Nevertheless, the role of the Gal-3/CD98 axis in atrial arrhythmogenesis is unclear. In this study, we investigated the effects of Gal-3/CD98 signalling on atrial pathogenesis.Whole cell patch clamp and western blotting were used to analyse calcium/potassium homeostasis and calcium-related signalling in Gal-3-administrated HL-1 atrial cardiomyocytes with/without CD98 neutralized antibodies. Telemetry electrocardiographic recording, Masson's trichrome staining and immunohistochemistry staining of atrium were obtained from mice having received tail-vein injections with Gal-3.Gal-3-treated HL-1 myocytes had a shorter action potential duration, smaller L-type calcium current, increased sarcoplasmic reticulum (SR) calcium content, NaGal-3 recombinant protein administration increases atrial fibrosis and arrhythmogenesis through CD98 signalling. Targeting Gal-3/CD98 axis might be a novel therapeutic strategy for patients with AF and high Gal-3 levels.

Fibroblast growth factor (FGF)-23 induces hypertrophy and calcium (Ca2+) dysregulation in cardiomyocytes, leading to cardiac arrhythmia and heart failure. However, knowledge regarding the effects of FGF-23 on cardiac fibrogenesis remains limited. This study investigated whether FGF-23 modulates cardiac fibroblast activity and explored its underlying mechanisms. We performed MTS analysis, 5-ethynyl-2′-deoxyuridine assay, and wound-healing assay in cultured human atrial fibroblasts without and with FGF-23 (1, 5 and 25 ng/mL for 48 h) to analyze cell proliferation and migration. We found that FGF-23 (25 ng/mL, but not 1 or 5 ng/mL) increased proliferative and migratory abilities of human atrial fibroblasts. Compared to control cells, FGF-23 (25 ng/mL)-treated fibroblasts had a significantly higher Ca2+ entry and intracellular inositol 1,4,5-trisphosphate (IP3) level (assessed by fura-2 ratiometric Ca2+ imaging and enzyme-linked immunosorbent assay). Western blot analysis showed that FGF-23 (25 ng/mL)-treated cardiac fibroblasts had higher expression levels of calcium release-activated calcium channel protein 1 (Orai1) and transient receptor potential canonical (TRPC) 1 channel, but similar expression levels of α-smooth muscle actin, collagen type IA1, collagen type Ⅲ, stromal interaction molecule 1, TRPC 3, TRPC6 and phosphorylated-calcium/calmodulin-dependent protein kinase II when compared with control fibroblasts. In the presence of ethylene glycol tetra-acetic acid (a free Ca2+ chelator, 1 mM) or U73122 (an inhibitor of phospholipase C, 1 μM), control and FGF-23-treated fibroblasts exhibited similar proliferative and migratory abilities. Moreover, polymerase chain reaction analysis revealed that atrial fibroblasts abundantly expressed FGF receptor 1 but lacked expressions of FGF receptors 2-4. FGF-23 significantly increased the phosphorylation of FGF receptor 1. Treatment with PD166866 (an antagonist of FGF receptor 1, 1 μM) attenuated the effects of FGF-23 on cardiac fibroblast activity. In conclusion, FGF-23 may activate FGF receptor 1 and subsequently phospholipase C/IP3 signaling pathway, leading to an upregulation of Orai1 and/or TRPC1-mediated Ca2+ entry and thus enhancing human atrial fibroblast activity.

While the effects of environmental factors (e.g., coexisting organic macromolecules and solar irradiation) on the phase transformation and oxidative dissolution of chemically exfoliated molybdenum nanosheets (ceMoS

The ketogenic diet (KD) might improve cardiac function in diabetic cardiomyopathy, but the mechanisms remain unclear. This study investigated the effects of KD on myocardial fatty acid (FA), glucose, and ketone metabolism in diabetic cardiomyopathy. Echocardiograms, biochemistry, and micro-positron emission tomography were performed to evaluate cardiac function and glucose uptake in control rats and streptozotocin-induced diabetes mellitus (DM) rats with normal diet (ND) or KD for 6 weeks. Histopathology, adenosine triphosphate measurement, and Western blot were performed in the ventricular myocytes to analyze fibrosis, FA, ketone body, and glucose utilization. The ND-fed DM rats exhibited impaired left ventricular systolic function and increased chamber dilatation, whereas control and KD-fed DM rats did not. The KD reduced myocardial fibrosis and apoptosis in the DM rats. Myocardial glucose uptake in the micro-positron emission tomography was similar between ND-fed DM rats and KD-fed DM rats and was substantially lower than the control rats. Compared with the control rats, ND-fed DM rats had increased phosphorylation of acetyl CoA carboxylase and higher expressions of CD-36, carnitine palmitoyltransferase-1β, tumor necrosis factor-α, interleukin-1β, interleukin6, PERK, and e-IF2α as well as more myocardial fibrosis and apoptosis (assessed by Bcl-2, BAX, and caspase-3 expression); these increases were attenuated in the KD-fed DM rats. Moreover, ND-fed DM rats had significantly lower myocardial adenosine triphosphate, BHB, and OXCT1 levels than the control and KD-fed DM rats. The KD may improve the condition of diabetic cardiomyopathy by suppressing FA metabolism, increasing ketone utilization, and decreasing endoplasmic reticulum stress and inflammation.

Tumour necrosis factor (TNF)‐α induces cardiac metabolic disorder and mitochondrial dysfunction. Hydrogen sulphide (H2S) contains anti‐inflammatory and biological effects in cardiomyocytes. This study investigated whether H2S modulates TNF‐α‐dysregulated mitochondrial function and metabolism in cardiomyocytes. HL‐1 cells were incubated with TNF‐α (25 ng/mL) with or without sodium hydrosulphide (NaHS, 0.1 mmol/L) for 24 hours. Cardiac peroxisome proliferator‐activated receptor (PPAR) isoforms, pro‐inflammatory cytokines, receptor for advanced glycation end products (RAGE) and fatty acid metabolism were evaluated through Western blotting. The mitochondrial oxygen consumption rate and adenosine triphosphate (ATP) production were investigated using Seahorse XF24 extracellular flux analyzer and bioluminescence assay. Fluorescence intensity using 2′, 7′‐dichlorodihydrofluorescein diacetate was used to evaluate mitochondrial oxidative stress. NaHS attenuated the impaired basal and maximal respiration, ATP production and ATP synthesis and enhanced mitochondrial oxidative stress in TNF‐α‐treated HL‐1 cells. TNF‐α‐treated HL‐1 cells exhibited lower expression of PPAR‐α, PPAR‐δ, phosphorylated 5′ adenosine monophosphate‐activated protein kinase‐α2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase‐1, PPAR‐γ coactivator 1‐α and diacylglycerol acyltransferase 1 protein, but higher expression of PPAR‐γ, interleukin‐6 and RAGE protein than control or combined NaHS and TNF‐α‐treated HL‐1 cells. NaHS modulates the effects of TNF‐α on mitochondria and the cardiometabolic system, suggesting its therapeutic potential for inflammation‐induced cardiac dysfunction.

Gene amplified in esophageal cancer 1 (GAEC1) expression and copy number changes are frequently associated with the pathogenesis of colorectal carcinomas. The current study aimed to identify the pathway and its transcriptional factors with which GAEC1 interacts within colorectal cancer, to gain a better understanding of the mechanics by which this gene exercises its effect on colorectal cancer. Two colonic adenocarcinoma cell lines (SW48 and SW480) and a nonneoplastic colon epithelial cell line (FHC) were transfected with GAEC1 to assess the oncogenic potential of GAEC1 overexpression. Multiple in vitro assays, including cell proliferation, wound healing, clonogenic, apoptosis, cell cycle, and extracellular flux, were performed. Western blot analysis was performed to identify potential gene-interaction partners of GAEC1 in vitro. Results showed that the overexpression of GAEC1 significantly increased cell proliferation, migration, and clonogenic potential ( P

Background Glucose monitoring is vital for glycemic control in patients with diabetes mellitus (DM). Continuous glucose monitoring (CGM) measures whole-day glucose levels. Hemoglobin A1c (HbA1c) is a vital outcome predictor in patients with DM. Methods This study investigated the relationship between HbA1c and CGM, which remained unclear hitherto. Data of patients with DM (n = 91) who received CGM and HbA1c testing (1–3 months before and after CGM) were retrospectively analyzed. Diurnal and nocturnal glucose, highest CGM data (10%, 25%, and 50%), mean amplitude of glycemic excursions (MAGE), percent coefficient of variation (%CV), and continuous overlapping net glycemic action were compared with HbA1c values before and after CGM. Results The CGM results were significantly correlated with HbA1c values measured 1 (r = 0.69) and 2 (r = 0.39) months after CGM and 1 month (r = 0.35) before CGM. However, glucose levels recorded in CGM did not correlate with the HbA1c values 3 months after and 2–3 months before CGM. MAGE and %CV were strongly correlated with HbA1c values 1 and 2 months after CGM, respectively. Diurnal blood glucose levels were significantly correlated with HbA1c values 1–2 months before and 1 month after CGM. The nocturnal blood glucose levels were significantly correlated with HbA1c values 1–3 months before and 1–2 months after CGM. Conclusions CGM can predict HbA1c values within 1 month after CGM in patients with DM.

Sarcopenia, the age-associated-fragility with loss of skeletal muscle mass and function, often coexists with type 2 diabetes (T2D) in older individuals. Derangement of muscle metabolism and mitochondrial dynamics is critical, particularly in high-energy-demand organs in patients with metabolic disorder. However, targeted therapies to halt or reverse the pathological progression of sarcopenia coexisting with T2D are unavailable. Studies have identified the pathological roles of class I histone deacetylases (HDACs) in both T2D and sarcopenia. In addition to their proinflammatory properties, HDACs are known to modify muscle metabolism and mitochondrial dynamics in both the development of sarcopenia and pathogenesis of diabetes. Proper quality control of mitochondrial dynamics through protein degradation and the synthesis of new proteins may improve skeletal muscle function in sarcopenia. Class I HDAC inhibitors improve energy metabolism and modulate autophagy-related genes in skeletal muscle. However, class IIa HDAC4 plays a protective role in preserving skeletal muscle structure following long-term denervation, and selective inhibition of class IIa HDAC activity had no impact on oxidative metabolism of muscle mitochondria. These findings suggest the vital role of class I HDAC modulation in bioenergetics and mitochondria quality control, and may lead to a novel therapeutic strategy targeting sarcopenia that coexists with T2D. HDAC inhibitors have been approved for clinical applications, and interventions targeting on HDACs may be promising for the treatment of sarcopenia.

Fructose is a main dietary sugar involved in the excess sugar intake-mediated progression of cardiovascular diseases and cardiac arrhythmias. Chronic intake of fructose has been the focus on the possible contributor to the metabolic diseases and cardiac inflammation. Recently, the small intestine was identified to be a major organ in fructose metabolism. The overconsumption of fructose induces dysbiosis of the gut microbiota, which, in turn, increases intestinal permeability and activates host inflammation. Endotoxins and metabolites of the gut microbiota, such as lipopolysaccharide, trimethylamine N-oxide, and short-chain fatty acids, also influence the host inflammation and cardiac biofunctions. Thus, high-fructose diets cause heart–gut axis disorders that promote cardiac arrhythmia. Understanding how gut microbiota dysbiosis-mediated inflammation influences the pathogenesis of cardiac arrhythmia may provide mechanisms for cardiac arrhythmogenesis. This narrative review updates our current understanding of the roles of excessive intake of fructose on the heart-gut axis and proposes potential strategies for inflammation-associated cardiac vascular diseases.

This study aims to investigate the overexpression-induced properties of tumor suppressor FAM134B (family with sequence similarity 134, member B) in colon cancer, examine the potential gene regulators of FAM134B expression and its impact on mitochondrial function. FAM134B was overexpressed in colon cancer and non-neoplastic colonic epithelial cells. Various cell-based assays including apoptosis, cell cycle, cell proliferation, clonogenic, extracellular flux and wound healing assays were performed. Western blot analysis was used to confirm and identify potential interacting partners of FAM134B in vitro. Immunohistochemistry and qPCR were employed to determine the expressions of MIF and FAM134B, respectively, on 63 patients with colorectal carcinoma. Results showed that FAM134B is involved in the cell cycle and mitochondrial function of colon cancer. Overexpression of FAM134B was coupled with increased expression levels of APC, p53, and MIF. Increased expression of both APC and p53 further validates the potential role of tumor suppressor FAM134B in regulating cancer progression through the WNT/ß-catenin signaling pathway. In approximately 70% of the patients with colorectal cancer, FAM134B downregulation was correlated with MIF protein overexpression while the remaining 30% showed concurrent expression of FAM134B and MIF (P = .045). High expression of MIF coupled with low expression of FAM134B is associated with microsatellite instability status in colorectal carcinomas (P = .049). FAM134B may exert its tumor suppressive function through affecting cell cycle, mitochondrial function via potentially interacting with MIF and p53.

Fruit and vegetable wastes contribute to a substantial proportion of global food waste. While these wastes could potentially be repurposed for a wide range of applications, the majority of them are discarded without effective utilization. To address the current challenges of fruit waste accumulation and sustainable nanomaterial synthesis, natural reductants derived from discarded dragon fruit (Hylocereus polyrhizus) peels are proposed as an alternative to conventional hazardous reductants for graphene-based material synthesis. Given that the chemical reduction of graphene oxide (GO) is the major route for graphene production, the effectiveness of the proposed reductants derived from peels of dragon fruit on graphene oxide reduction was evaluated. The reducing constituents (i.e., betanin substances) were recovered from dragon fruit peel wastes using facile aqueous extraction processes, where suitable extraction treatments (e.g., pH conditions) were found to be critical for boosting the reducing power of the obtained reductants. The compiled results indicated that the proposed fruit waste-derived reducing agents demonstrated great promise for GO reduction through S

In the present work, a novel reduced graphene oxide (rGO)-based electrochemical sensor has been developed for the detection of sulfamethoxazole (SMZ) using differential pulse voltammetry. Ascorbic acid (AA) under acid conditions has proven to be an efficient yet environmentally benign reductant to recover the outstanding electrochemical activity of graphene. Additionally, the ascorbic-acid-reduced graphene oxide exhibits a high total removal rate of epoxide and hydroxyl functional groups, with a rich presence of carbonyl and carboxyl functional groups, allowing an excellent solution processing ability for realizing further functionalization and applications, unlike reduced graphene oxide produced by conventional harmful reductants (e.g., hydrazine). Moreover, excellence in the determination of SMZ is likely due to selective reduction of oxygen functional groups on the graphene basal planes by ascorbic acid, which enhances π–π interactions with SMZ, which is present in anionic forms in natural aqueous systems. The AArGO-modified electrodes achieved a linear range of 0.5–50 μM with a limit of detection of 0.04 μM and satisfied recoveries in different water samples. Additionally, the cationic surfactant (e.g., cetyltrimethylammonium bromide, CTAB) showed a promoting effect toward SMZ determination. Collectively, the AArGO modified electrodes showed great improvement in the anodic oxidation reactivity of SMZ with high selectivity and stability, allowing promising and feasible applications in on-site environmental monitoring.

Histone deacetylases (HDACs) play vital roles in the pathophysiology of heart failure, which is associated with mitochondrial dysfunction. Tumor necrosis factor-α (TNF-α) contributes to the genesis of heart failure and impairs mitochondria. This study evaluated the role of HDACs in TNF-α-induced mitochondrial dysfunction and investigated their therapeutic potential and underlying mechanisms. We measured mitochondrial oxygen consumption rate (OCR) and ATP production using Seahorse XF24 extracellular flux analyzer and bioluminescent assay in control and TNF-α (10 ng/ml, 24 h)-treated HL-1 cells with or without HDAC inhibition. TNF-α increased Class I and II (but not Class IIa) HDAC activities (assessed by Luminescent) with enhanced expressions of Class I (HDAC1, HDAC2, HDAC3, and HDAC8) but not Class IIb HDAC (HDAC6 and HDAC10) proteins in HL-1 cells. TNF-α induced mitochondrial dysfunction with impaired basal, ATP-linked, and maximal respiration, decreased cellular ATP synthesis, and increased mitochondrial superoxide production (measured by MitoSOX red fluorescence), which were rescued by inhibiting HDACs with MPT0E014 (1 μM, a Class I and IIb inhibitor), or MS-275 (1 μM, a Class I inhibitor). MPT0E014 reduced TNF-α-decreased complex I and II enzyme (but not III or IV) activities (by enzyme activity microplate assays). Our results suggest that Class I HDAC actions contribute to TNF-α-induced mitochondrial dysfunction in cardiomyocytes with altered complex I and II enzyme regulation. HDAC inhibition improves dysfunctional mitochondrial bioenergetics with attenuation of TNF-α-induced oxidative stress, suggesting the therapeutic potential of HDAC inhibition in cardiac dysfunction.

GAEC1 (gene amplified in oesophageal cancer 1) is a transforming oncogene with tumorigenic potential observed in both oesophageal squamous cell carcinoma and colorectal cancer. Nonetheless, there has been a lack of study done on this gene to understand how this gene exert its oncogenic properties in cancer. This study aims to identify novel mutation sites in GAEC1. To do so, seventy-nine matched colorectal cancers were tested for GAEC1 mutation via Sanger sequencing. The mutations noted were investigated for the correlations with the clinicopathological parameters of the patients with the cancer. Additionally, GAEC1 copy number aberration (CNA), mRNA and protein expression were determined with the use of droplet digital (dd) polymerase chain reaction (PCR), real-time PCR and Western blot (confirmed with immunofluorescence analysis). GAEC1 mutation was noted in 8.8% (n = 7/79) of the cancer tissues including one missense mutation, four loss of heterozygosity (LOH) and two substitutions. These mutations were significantly associated with cancer perforation (p = 0.021). GAEC1 mutation is frequently associated with increased GAEC1 protein expression. Nevertheless, GAEC1 mRNA and protein are only weakly associated. Taken together, GAEC1 mutation affects GAEC1 expression and is associated with poorer clinical outcomes. This further strengthens the role of GAEC1 as an oncogene.

This study was to investigate the expression pattern, mechanisms and clinicopathological implications of miR-193a-3p in colorectal cancer. Fresh-frozen tissues from 70 matched colorectal adenocarciomas and the adjacent non-neoplastic mucosae were prospectively collected. Two colorectal cancer cell lines (SW480 and SW48) and a non-neoplastic colon cell line (FHC) were also used. The expression levels of miR193a-3p in the cells and tissues were measured by quantitative real-time polymerase chain reaction. The expression of KRAS protein as a predicted downstream target for miR-193a was studied by immunohistochemistry. Restoration of the miR-193a level in the cell lines by permanent transfection was achieved and multiple functional and immunological assays were performed to analyze the functions of miR-193a in vitro. Down-regulation of miR-193a-3p was noted in 70% of the colorectal cancer tissues when compared to non-neoplastic colorectal tissues. In addition, down-regulation of miR-193a was significantly correlated with carcinoma of early stages (P

Heme, a molecule abundant in red meat, is assumed to exert carcinogenic effects on normal colonic cells and tumour suppressive effects on cancer cells, though the hypothesis has not been explicitly proven yet. The present study aims to investigate hemin induced cytotoxic, genetic and biological alterations in both normal and cancerous colonic epithelial cells, which may imply its carcinogenic and anticarcinogenic properties. Normal colonic epithelial cells and colon carcinoma cells were treated with a 0-500 µM concentration of hemin for 1-4 days following which cytotoxicity and wound healing assays, western blot, rt-PCR and cell cycle analysis were performed. Interestingly, hemin was cytotoxic to normal colonic cells, but carcinoma cells were more resistant. Cell migration potential of both normal colonic cells and colon carcinoma cells was impeded by hemin. Hemin caused upregulation of both P53 and β-catenin gene and proteins expression in normal colonic cells with concomitant cell cycle arrest at G1(Gap 1) and G2/M (Gap 2/ Mitosis). G1 and G2 cell cycle arrests were also observed in colon carcinoma cells. In conclusion, the present study confirms that hemin, a main heme molecule present in red meat, facilitates behavioural, genetic and cell cycle kinetic alterations in both normal colonic epithelial and colon carcinoma cells.

Background Receptor for advanced glycation end products (RAGE) signaling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression. This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes. Methods Western blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N-terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL-1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor-κB (NF-κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 hours. Results Calcitriol (10 nM) significantly reduced RAGE protein expression and increased sRAGE concentrations in HL-1 cardiomyocytes compared with control cells. These changes were associated with increased protein expression and enzyme activity of ADAM10 and higher mRNA expression of esRAGE. In the presence of ADAM10 inhibitor, however, the suppressive effect of calcitriol on RAGE was diminished. Methylglyoxal (500 μM for 10 min)-mediated JNK phosphorylation was attenuated in the presence of calcitriol (10 nM). Moreover, control and NF-κB inhibitor-treated HL-1 cells had similar RAGE and sRAGE expression, suggesting that calcitriol-mediated RAGE modulation was independent of NF-κB signaling. Conclusions We showed that RAGE downregulation and increased sRAGE production by calcitriol was mediated through ADAM10 activation in cardiomyocytes. The results suggest that calcitriol has therapeutic potential in treating RAGE-mediated cardiovascular complications. This article is protected by copyright. All rights reserved.

FAM134B is a putative tumour suppressor gene and no mutations in FAM134B have been reported in colorectal cancer (CRC) to date. This study aims to identify FAM134B mutation sites and the clinicopathological significance of the gene in patients with CRC. Eighty-eight colorectal cancers were studied for FAM134B mutations by Sanger sequencing. The mutations in these cancers were then tested for correlations with the clinical and pathological parameters of the studied cancers. In addition, mRNA and protein expression of FAM134B in colorectal cancers was examined by polymerase chain reaction, Western blots, and immunofluorescence analysis. FAM134B mutation was noted in 46.5% (41/88) of patients with CRC. Thirty-one novel potentially pathogenic mutations were noted in coding and intronic regions of FAM134B in CRC, the majority of which were single-nucleotide substitutions. Of the 31 mutations, eight novel frameshift mutations showed potential to cause non-sense-mediated mRNA decay (NMD) in computational analysis. In addition, FAM134B mutations were associated with various clinical and pathological variables, including sex of the patients, presence of metachronous cancer, size, T staging, presence of distant metastases, and positivity of microsatellite instability (MSI) in the cancer (p

Colonic microbiota play important roles in the development of colorectal cancer. We aim to characterise the mucosa-associated microbiota in the tumour as well as the matched non-neoplastic mucosa from patients with colorectal cancer. Microbiota profiling in these samples was done using high-throughput 16S rRNA amplicon sequencing. Our results showed that the microbiota richness and diversity were similar between the tumour and non-neoplastic mucosae. Linear discriminant analysis effect size (LEfSe) analysis identified Fusobacterium and Campylobacter as the key genera of the tumour while Brevundimonas as the key genus of the non-neoplastic mucosa. In patients with shorter survival period, the relative abundance of Fusobacterium and Campylobacter was significantly higher in the tumour. Besides, regardless of the sites, tumour showed higher abundance of Fusobacterium. On the other hand, the relative abundance of Brevundimonas was significantly lower in the tumour. When validated with quantitative ddPCR, we found the absolute numbers of both Fusobacterium and F. nucleatum were significantly higher in the carcinoma from patients with shorter survival period, conventional type of adenocarcinoma in the distal portion of the large intestine (descending colon, sigmoidal colon, and rectum). In conclusion, our study showed a compositional alteration in the mucosa-associated microbiota in the tumour, which may contribute to the progression of colorectal cancer.

Layered transition metal dichalcogenides, including molybdenum disulfide (MoS2), have previously been considered stable in the ambient environment due to the absence of dangling bonds in the electr...

The vital need for Akt in maintaining basic cellular function has highlighted its importance in carcinogenesis. Unfortunately, Akt inhibitor development outcome has remained poor, as most of them have failed to show significant clinical benefit to cancer patients during the clinical trials. Recently, a new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), which show high tissue specificity, have demonstrated great influence in cancer progression and/or cancer inhibition. As both Akt signalling pathways and lncRNAs play such innate roles in carcinogenesis, identifying the specific roles that these lncRNAs play within this pathway may represent a novel research avenue for developing Akt inhibitors with better therapeutic properties. In addition, understanding the diverse mechanism by which lncRNAs regulate gene expression can assist in deciphering the fundamentals of carcinogenesis. The focus of interest should be on the lncRNAs, which affect Akt and finding the link between lncRNAs and Akt pathways associated with carcinogenesis. LncRNAs within the Akt pathways could affect multiple pathways in a particular cancer type, which ultimately creates an intricate web of connections between the pathways. In summary, lncRNAs have tremendous potential in cancer diagnosis, assessing cancer patient prognosis and in developing new therapeutic options for patients with resistance to current cancer therapies. Thus, understanding how lncRNAs influence the Akt pathway is essential for the development of novel and effective cancer therapies.