Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with ...respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L).
Despite advances in cancer detection and therapy, it has been estimated that the incidence of cancers will increase, while the mortality rate will continue to remain high, a fact explained by the ...large number of patients diagnosed in advanced stages when therapy is often useless. Therefore, it is necessary to invest knowledge and resources in the development of new non-invasive biomarkers for the early detection of cancer and new therapeutic targets for better health management. In this review, we provided an overview on the collagen family as promising biomarkers and on how they may be exploited as therapeutic targets in cancer. The collagen family tridimensional structure, organization, and functions are very complex, being in a tight relationship with the extracellular matrix, tumor, and immune microenvironment. Moreover, accumulating evidence underlines the role of collagens in promoting tumor growth and creating a permissive tumor microenvironment for metastatic dissemination. Knowledge of the molecular basis of these interactions may help in cancer diagnosis and prognosis, in overcoming chemoresistance, and in providing new targets for cancer therapies.
Knockdown of KRT17 by siRNA induces antitumoral effects on gastric cancer cells Chivu-Economescu, Mihaela; Dragu, Denisa L.; Necula, Laura G. ...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association,
11/2017, Letnik:
20, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Background
Keratin 17 (KRT17) was shown to be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of various cancer types. Our previous studies identified ...KRT17 as a possible biomarker for gastric cancer by gene microarray, with an elevated expression that occurred early during tumorigenesis and increased during tumor progression. Based on these findings, we aimed to investigate KRT17 biological functions in gastric adenocarcinoma and its possible use as a rational molecular target for anticancer therapy.
Methods
We used RNA interference-mediated knockdown of KRT17 expression and analyzed the effects on cell proliferation, cell migration, and signal transduction in two gastric cell lines (AGS and NCI-N87) in vitro and on xenograft growth in vivo.
Results
The functional analysis of KRT17 knockdown cell lines showed a decreased cell proliferation (with 42.36% ± 3.2%) and migration ability (with 37.2% ± 6.2%) relative to scrambled siRNA control. The in vivo tumorigenicity on nude mice exhibited a significant decrease in tumor weight with 69.14% in xenografts obtained from AGS cells and 84.43% in xeno-NCI-N87 tumors. The analysis on KRT17 knockdown outcome on intracellular signaling identifies AKT/mTOR as the main affected pathway that sustains proliferation and survival, and also the AMPKα1/CREB pathway that was recently shown to induce organ protection and antiinflammatory response.
Conclusions
Our results highlight KRT17 as a possible biomarker in gastric cancer promoting tumor growth, motility, and invasion, and suggest that KRT17 can be a valuable molecular target for development of anti-gastric cancer-specific therapies.
Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. ...Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN (
= 8 × 10
), THBS2 (
= 1.2 × 10
), CTHRC1 (
= 1.1 × 10
), SULF1 (
= 3.8 × 10
), COL5A1 (
= 1.3 × 10
), COL10A1 (
= 5.7 × 10
), COL12A1 (
= 2 × 10
) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (
-value range 4.82 × 10
-1.63 × 10
). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets.
Metabolic syndrome is associated with increased risk of cardiovascular disease. This study investigated the correlation between adipocyte and inflammation biomarkers, and metabolic syndrome and its ...components. The study included 80 patients with normal body-mass index and 80 obese patients. The groups were assessed for serum values of adiponectin, leptin and highly sensitive C reactive protein (hsCRP), the homeostatic model assessment of insulin resistance (HOMA-IR), as well as the influence of these biochemical markers on the prevalence of metabolic syndrome and its components. Leptin, HOMA-IR and hsCRP had statistically significant (P<0.01) higher values in the group of obese subjects, while adiponectin had statistically significant (P<0.01) lower values. The prevalence of metabolic syndrome was 35% in the obese group and 5% in the normal weight group. Adiponectin and HOMA-IR were the variables significantly associated with metabolic syndrome (P<0.01), adiponectin/HOMA-IR ratio and leptin/adiponectin ratio were also associated with metabolic syndrome (P<0.01). No relationship was found between metabolic syndrome and hsCRP. Adiponectin and adiponectin/HOMA-IR were associated with all the components of metabolic syndrome and they can be useful to identify patients with high risk of diabetes mellitus and cardiovascular disease.
Obesity and overweight are major contributors to the morbidity and mortality of modern civilization. This study determined the prevalence of certain risk factors for adiposity and assesses their ...impact on overweight/obesity prevalence. Nine hundred individuals were evaluated, aged between 18-65 years, including clinical examination, evaluation of medical history, BMI determination and completion on questionnaires assessing nutritional intake and presence of depression symptoms. Overweight prevalence was 29.56% and obesity prevalence was 21.33%. Fast-food consumption was the most frequent risk factor for adiposity found in 61.67% of individuals, eating <3 meals/day was found in 58.89%, sedentary lifestyle in 53.33%, sleeping time <6 h/day in 44.22%, hypercaloric nutrition in 43.56%, excessive alcohol consumption in 42.89% and depression symptoms in 31.78%. Unhealthy lifestyle a composite risk factor was identified in 67.33% of individuals. Fast-food consumption increases the risk for adiposity by 1.85-fold while sedentary lifestyle by 1.79-fold. Risk factors for adiposity play an important role in increasing the prevalence of overweight and obesity. Public health measures are necessary in order to educate the general population regarding the importance of healthy nutrition and physical exercise.
In the recent years a special attention has been given to a major health concern namely to male infertility, defined as the inability to conceive after 12 months of regular unprotected sexual ...intercourse, taken into account the statistics that highlight that sperm counts have dropped by 50–60% in recent decades. According to the WHO, infertility affects approximately 9% of couples globally, and the male factor is believed to be present in roughly 50% of cases, with exclusive responsibility in 30%. The aim of this article is to present an evidence-based approach for diagnosing male infertility that includes finding new solutions for diagnosis and critical outcomes, retrieving up-to-date studies and existing guidelines. The diverse factors that induce male infertility generated in a vast amount of data that needed to be analyzed by a clinician before a decision could be made for each individual. Modern medicine faces numerous obstacles as a result of the massive amount of data generated by the molecular biology discipline. To address complex clinical problems, vast data must be collected, analyzed, and used, which can be very challenging. The use of artificial intelligence (AI) methods to create a decision support system can help predict the diagnosis and guide treatment for infertile men, based on analysis of different data as environmental and lifestyle, clinical (sperm count, morphology, hormone testing, karyotype, etc.), and “omics” bigdata. Ultimately, the development of AI algorithms will assist clinicians in formulating diagnosis, making treatment decisions, and predicting outcomes for assisted reproduction techniques. Summary Sentence The article intends to present an evidence-based approach for the diagnosis of male infertility. These involve many molecular aspects and the necessity of artificial intelligence techniques for diagnosis prediction and treatment guidance. Graphical Abstract
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