Explore the vast range of titles available.

Autophagy is a conserved cellular process required to maintain homeostasis. The hallmark of autophagy is the formation of a phagophore that engulfs cytosolic materials for degradation and recycling to synthesize essential components. Basal autophagy is constitutively active under normal conditions and it could be further induced by physiological stimuli such as hypoxia, nutrient starvation, endoplasmic reticulum stress,energy depletion, hormonal stimulation and pharmacological treatment. In cancer, autophagy is highly context-specific depending on the cell type, tumour microenvironment, disease stage and external stimuli. Recently, the emerging role of autophagy as a double-edged sword in cancer has gained much attention. On one hand, autophagy suppresses malignant transformation by limiting the production of reactive oxygen species and DNA damage during tumour development. Subsequently, autophagy evolved to support the survival of cancer cells and promotes the tumourigenicity of cancer stem cells at established sites. Hence, autophagy is an attractive target for cancer therapeutics and researchers have been exploiting the use of autophagy modulators as adjuvant therapy. In this review, we present a summary of autophagy mechanism and controlling pathways, with emphasis on the dual-role of autophagy (double-edged sword) in cancer. This is followed by an overview of the autophagy modulation for cancer treatment and is concluded by a discussion on the current perspectives and future outlook of autophagy exploitation for precision medicine.

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra , Fusobacterium nucleatum , Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra , Fusobacterium nucleatum , Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Cancer is a global health problem associated with genetics and unhealthy lifestyles. Increasingly, pathogenic infections have also been identified as contributors to human cancer initiation and progression. Most pathogens (bacteria, viruses, fungi, and parasites) associated with human cancers are categorized as Group I human carcinogens by the International Agency for Research on Cancer, IARC. These pathogens cause carcinogenesis via three known mechanisms: persistent infection that cause inflammation and DNA damage, initiation of oncogene expression, and immunosuppression activity of the host. In this review, we discuss the carcinogenesis mechanism of ten pathogens, their implications, and some future considerations for better management of the disease. The pathogens and cancers described are Helicobacter pylori (gastric cancer), Epstein-Barr virus (gastric cancer and lymphoma), Hepatitis B and C viruses (liver cancer), Aspergillus spp. (liver cancer), Opisthorchis viverrine (bile duct cancer), Clonorchis sinensis (bile duct cancer), Fusobacterium nucleatum (colorectal cancer), Schistosoma haematobium (bladder cancer); Human Papillomavirus (cervical cancer), and Kaposi’s Sarcoma Herpes Virus (Kaposi’s sarcoma).

Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE). It is caused by immune dysregulation and kidney inflammation. In recent findings, gut microbiota potentially acts as primary mediators to enhance immune complex deposition, complement activation, and macrophage infiltration, and led to renal inflammation. Gut inflammation, known as leaky gut, allows pathogenic bacteria to enter the blood stream to form immune complexes which deposit on the kidney. Lymphocytes and macrophages induct a proinflammatory cytokine milieu that leads to kidney inflammation. Accumulating pieces of evidence from the field of gender bias, dietary habit, alcohol, smoking and antibiotic consumption were closely related to dysbiosis of gut microbiota in SLE. However, little is known about the causes of gut microbiota dysbiosis and the potential pathway that leads to lupus nephritis (LN) flare. In this review, we will bring into deeper insight for the potential link of gut microbiota on immune system with a particular focus on renal inflammation. Moreover, we also discuss the potential novel therapies that regulate gut composition to improve or complement the current treatment of LN.

Vitamin A and E are indispensable fat-soluble vitamins that play pivotal roles in promoting human health and well-being. Accurate quantification of these vitamins in biological samples is critical. Thus, we aim to develop and optimise a sensitive method suitable for simultaneous analysis of vitamin A and E. We introduced a method for simultaneous detection of Vitamin A and E using reverse-phase high-performance liquid chromatography (RP-HPLC). Calibration curves and quality control samples were prepared using a 4% of Bovine Serum Albumin (BSA) matrix. The analytes and internal standard (ISTD), Dodecanophenone were effectively separated using a polar column and detected via UV detector at wavelengths of 255 nm, 298 nm, and 325 nm respectively, with a total run time of 30 min. Results: The method demonstrated excellent linearity with regression coefficients (r²) > 0.995. The optimisation process of the HPLC method affirmed its precision and reliability, meeting analytical chemistry standards. Subsequently, this validated method was applied to serum samples obtained from patients and a population cohort exhibiting distinct clinical pathologies, including individuals without colorectal cancer (CRC), those with symptomatic and asymptomatic CRC. Conclusions: In conclusion, this HPLC method offers a reliable means for routine quantification of vitamin A and E in human serum, holding promise for enhancing nutritional research and clinical diagnostics. Its novelty lies in the use of a surrogate BSA matrix with a polar RP-HPLC column and multi-wavelength detection, enabling robust quantification of endogenous analytes in clinically relevant cohorts.

Food and diet are critical risk factors for colorectal cancer (CRC). Food environments (FEs) can contribute to disease risk, including CRC. This review investigated the link between FEs and CRC incidence and mortality risk. The systematic search of studies utilised three primary journal databases: PubMed, Scopus, and Web of Science. Retrieved citations were screened and the data were extracted from articles related to the FE-exposed populations who were at risk for CRC and death. We evaluated ecological studies and cohort studies with quality assessment and the Newcastle-Ottawa Quality Assessment Form for Cohort Studies, respectively. A descriptive synthesis of the included studies was performed. Out of 89 articles identified, eight were eligible for the final review. The included studies comprised six ecological studies and two cohort studies published from 2013 to 2021. Six articles were from the US, one was from Africa, and one was from Switzerland. All eight studies were of good quality. The significant finding was that CRC incidence was associated with the availability of specific foods such as red meat, meat, animal fats, energy from animal sources, and an unhealthy FE. Increased CRC mortality was linked with the availability of animal fat, red meat, alcoholic beverages, and calorie food availability, residence in food deserts, and lower FE index. There were a variety of associations between CRC and the FE. The availability of specific foods, unhealthy FE, and food desserts impact CRC incidence and mortality. Creating a healthy FE in the future will require focus and thorough planning.

The burden of colorectal cancer (CRC) is increasing worldwide especially in developing countries. This phenomenon may be attributable to lifestyle, dietary and environmental risk factors. We aimed to determine the level of 25 trace elements, their interaction with environmental risk factors, and subsequently develop a risk prediction model for CRC (RPM CRC). For the discovery phase, we used a hospital-based case–control study (CRC and non-CRC patients) and in the validation phase we analysed pre-symptomatic samples of CRC patients from The Malaysian Cohort Biobank. Information on the environmental risk factors were obtained and level of 25 trace elements measured using the ICP-MS method. CRC patients had lower Zn and Se levels but higher Li, Be, Al, Co, Cu, As, Cd, Rb, Ba, Hg, Tl, and Pb levels compared to non-CRC patients. The positive interaction between red meat intake ≥ 50 g/day and Co ≥ 4.77 µg/L (AP 0.97; 95% CI 0.91, 1.03) doubled the risk of CRC. A panel of 24 trace elements can predict simultaneously and accurate of high, moderate, and low risk of CRC (accuracy 100%, AUC 1.00). This study provides a new input on possible roles for various trace elements in CRC as well as using a panel of trace elements as a screening approach to CRC.

The human gut is home to complex microbial populations that change dynamically in response to various internal and external stimuli. The gut microbiota provides numerous functional benefits that are crucial for human health but in the setting of a disturbed equilibrium, the microbial community can cause deleterious outcomes such as diseases and cancers. Characterization of the functional activities of human gut microbiota is fundamental to understand their roles in human health and disease. Metaproteomics, which refers to the study of the entire protein collection of the microbial community in a given sample is an emerging area of research that provides informative details concerning functional aspects of the microbiota. In this mini review, we present a summary of the progress of metaproteomic analysis for studying the functional role of gut microbiota. This is followed by an overview of the experimental approaches focusing on fecal specimen for metaproteomics and is concluded by a discussion on the challenges and future directions of metaproteomic research.

Background: Trace elements play a pivotal role in Colorectal Cancer (CRC) inhibition and development process. This systematic review provides the basic comparison of case-control studies focusing on concentration of trace elements between those with CRC and controls Methods: The systematic review searched through two databases of Medline and Cochrane up to 24th June 2017. The search strategy focused on Population, Intervention, Comparison, and Outcomes (PICO). We searched the role of trace elements in cancer and focusing on case-control studies in CRC to obtain an insight into the differences in trace element concentrations between those with and without cancer. Results: The serum concentrations of Ca, Cu, Mg, Mn, Se, Si, and Zn were lower in CRC patients but for Co and S the levels were higher in CRC patients. The concentrations of Cd, Cr, Cu, Mg, Mn, Pb, and Zn were increased in patients with metastasis, but not in Se. As for colon tissue specimens, inconsistent levels were reported between studies, notably in Cu, Se, and Zn. No changes were reported for B and Ca levels. Most of the trace elements in the tissue specimens showed higher concentrations of Cr, Fe, K, Mg, P, Rb, S, and Si compared to Br. Conclusion: With the growing interest to understand the link between trace elements in carcinogenesis and the possible interactions, multi assessment analysis of a larger cohort of samples is necessary.

The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 h. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, and CSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin–proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial–mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, the present study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.