Current Molecular Medicine - Volume 20, Issue 1, 2020

Alzheimer's disease (AD) is a neurodegenerative disease and the main form of dementia, characterized by progressive cognitive decline and detrimental consequences in both personal-family and global level. Within this narrative review, we provide recent molecular aspects of Tau, a microtubule AD-associated protein, as well as amyloid beta, involved in AD pathophysiology. Moreover, we provide additional emerging data from basic research as well as clinical studies indicating an implicating role of gastrointestinal microbiota (GI-M), including Helicobacter pylori infection (Hp-I), in AD pathophysiology. Likewise, we identified through a molecular prism the current evidence of AD pathogenesis as well as its linkage with GI-M and emphasizing the role of Hp-I. All in all, additional large-scale studies are required for the further clarification of AD pathophysiology and its connection with GI-M and Hp-I, so as novel therapies on molecular basis become available.

In both men and women around the world, lung cancer accounts as the principal cause of cancer-related death after breast cancer. Therefore, early detection of the disease is a cardinal step in improving prognosis and survival of patients. Today, the newly-defined microRNAs regulate about 30 to 60 percent of the gene expression. Changes in microRNA Profiles are linked to numerous health conditions, making them sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation of microRNAs in real samples has proved to be rather challenging, which is largely attributable to the unique characteristics of these molecules. Short length, sequence similarity, and low concentration stand among the factors that define microRNAs. Recently, diagnostic technologies with a focus on wide-scale point of care have recently garnered attention as great candidates for early diagnosis of cancer. Electrochemical nano-biosensors have recently garnered much attention as a molecular method, showing great potential in terms of sensitivity, specificity and reproducibility, and last but not least, adaptability to point-of-care testing. Application of nanoscale materials in electrochemical devices as promising as it is, brings multiplexing potential for conducting simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling properties, these materials can be used to improve the efficiency of cancer diagnostics, offer more accurate predictions of prognosis, and monitor response to therapy in a more efficacious way. This article presents a concise overview of recent advances in the expeditiously evolving area of electrochemical biosensors for microRNA detection in lung cancer.

Malaria disease is a public health problem especially in tropical countries, 445.000 of malaria-related deaths have been reported in 2017. MicroRNAs (miRNAs) are small non-coding RNAs with 18-24 nucleotides in length, which have been demonstrated to regulate gene expression of several biological processes. The dysregulation of host immune-related gene expressions during the transcriptional process by microRNA has been extensively reported in malaria parasite invasion of erythrocytes infection. The candidate’s miRNAs would be used as potential biomarkers in the future and perspective. A systematic review on miRNAs as candidate clinical biomarkers in malaria infection has been established in this study. Electronic databases (Medline, EMBASE, CINAHL and Cochrane data bases) were screened and articles were included as per established selection criteria. We comprehensively searched to identify publications related to malaria and miRNA. PRISMA guidelines were followed, 262 articles were searched, duplicates and unconnected papers were excluded. Nineteen articles were included in the study. It was found that malaria parasite infected liver or tissue produce tissue-specific miRNAs and release to the blood stream. The association of miRNAs including miR-16, miR-155, miR-150, miR-451 and miR-223 with the dysregulations of immune-related genes expression such as PfEMP-1, IFN-γ, AGO- 1 AGO-2; IL4, CD80, CD86, CD36, ANG-1 and ANG-2 during early, severe and/or cerebral malaria infections indicate the potential use of those miRNAs as biomarkers for malaria infection.

Background: Adiponectin and 8-Hydroxy-2′-deoxyguanosine (8-OHdG) are identified as important biomarkers in the pathogenesis process of type 2 diabetes mellitus (T2DM). Whether adiponectin and 8-OHdG have a relation to cognitive decline in the elderly T2DM patients has been poorly understood. The aim of this study was to evaluate the effects of adiponectin and 8-OHdG in the elderly patients with T2DM and to determine the role of adiponectin and 8-OHdG in the cognitive impairment of the elderly patients with T2DM. Methods: 57 individuals were recruited and analyzed , with 26 cases of T2DM without cognitive impairment and 31 cases of T2DM with cognitive impairment. All of them underwent an examination of diabetes scales and blood glucose at different times. A primary diagnosis of diabetes was in line with the diagnosis criteria set by the American Diabetes Association (ADA). Statistical significance was defined as a P-value of less than 0.05. Results: The variables of sex, age, body mass index (BMI), hypertension, diabetes, metabolic syndrome, lacunar cerebral infarction, smoking and drinking in T2DM patients without cognitive impairment and with cognitive impairment showed no difference according to the univariate analysis exploring each variable separately (p>0.05). A significant difference was observed in the serum levels of adiponectin and 8-OHdG and the scales of MMSE and MoCA (p<0.05). Therefore, it was inferred that there is no correlation between glucose metabolic value and cognitive outcome of T2DM patients. Serum levels of adiponectin and 8-OHdG could act as biomarkers of cognitive impairment degree in the elderly T2DM patients. Conclusion: Serum levels of adiponectin and 8-OHdG could act as specific and sensitive biomarkers for the early diagnosis and treatment of cognitive impairment in elderly T2DM patients. Serum levels of adiponectin and 8-OHdG have a close relation to the neurological cognitive outcome of the elderly T2DM patients.

Purpose: Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model. Methods: All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC +PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining. Results: The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation. Conclusion: Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.

Background: Sarcopenia is characterized by the loss of muscle mass and strength (muscle atrophy) because of aging or chronic diseases, such as chronic liver disease (CLD). Different mechanisms are involved in skeletal muscle atrophy, including decreased muscle fibre diameter and myosin heavy chain levels and increased ubiquitin–proteasome pathway activity, oxidative stress and myonuclear apoptosis. We recently found that all these mechanisms, except myonuclear apoptosis, which was not evaluated in the previous study, were involved in muscle atrophy associated with hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLD. Objective: In the present study, we evaluated the involvement of myonuclear apoptosis in CLD-associated sarcopenia and the effect of N-acetyl cysteine (NAC) treatment on muscle strength and apoptosis, using a DDC-supplemented diet-fed mouse model. Methods: Four-month-old male C57BL6 mice were fed with a standard or DDCsupplemented diet for six weeks in the absence or presence of NAC treatment. Results: Our results showed that NAC attenuated the decrease in muscle fibre diameter and muscle strength associated with CLD-induced muscle wasting in gastrocnemius (GA) muscle of DDC-supplemented diet-fed mice. In addition, in GA muscle of the mice fed with DDC-supplemented diet-induced CLD showed increased myonuclear apoptosis compared with the GA muscle of the control diet-fed mice, as evidenced by increased apoptotic nuclei number, caspase-8 and caspase-9 expression, enzymatic activity of caspase-3 and BAX/BCL-2 ratio. NAC treatment inhibited all the mechanisms associated with myonuclear apoptosis in the GA muscle. Conclusion: To our knowledge, this is the first study which reports the redox regulation of muscle strength and myonuclear apoptosis in CLD-induced sarcopenia.

Background: Renal ischemia/reperfusion induces a systemic inflammatory response that is directly related to the development of cardiac hypertrophy due to cardiorenal syndrome type 3. Classic inflammatory pathways have been extensively investigated in cardiovascular diseases, including the participation of inflammasome in caspase-1-dependent IL-1β cleavage. Objective: In this study, we aimed to understand how lack of caspase-1 would impact the hypertrophic and apoptotic response in the heart after renal ischemia/reperfusion. Methods: Wildtype and caspase-1 knockout animals were submitted to a renal ischemia/reperfusion protocol. Briefly, left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 15 days. Gene expression was analysed by Real-Time PCR. Caspase activity was also evaluated. Results: Lack of caspase-1 led to a more pronounced cardiac hypertrophy in mice subjected to renal ischemia-reperfusion. Such hypertrophic process was accompanied by increased activity of caspase3/7 and 9, indicating apoptosis initiation in an IL-1β- independent manner. Conclusion: Our data corroborate important findings on the role of caspase-1 in the development of cardiac hypertrophy and remodeling.

Background: Bone defect caused by trauma, tumor resection, infection or congenital malformation is a common clinical disease. Bone tissue engineering is regarded as a promising way of bone defect reconstruction. Thus, agents that can promote osteogenesis have received great attention. Cytochalasin D (Cyto D), a metabolite derived from molds, proves to be able to modify actin, reorganize cytoskeleton, and then promote the osteogenic differentiation. Objective: The purpose of this study was to explore the effect and mechanism of Cyto D on osteogenic differentiation of mouse pre-osteoblast MC3T3-E1 cells. Methods: The optimum concentration of Cyto D was explored. The osteogenic differentiation of MC3T3-E1 cells induced by Cyto D was assessed by alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, western blotting and quantitative real-time polymerase chain reaction (RT-qPCR). In addition, a specific pathway inhibitor was utilized to explore whether MAPK pathways were involved in this process. Results: The results showed that the optimized concentration of action was 10-2μg/ml. The expression of Runx2, OCN and OSX was up-regulated by the supplement of Cyto D. ALP activity, calcium deposition, and phosphorylation level of p38 protein were also improved. Inhibition of the pathway significantly reduced the activation of p38, and the expression of osteogenic-related genes. Conclusion: Cyto D can promote the osteogenic differentiation of MC3T3 cells via the p38-MAPK signaling pathway, but not the ERK1/2 or JNK, and it is a potential agent to improve the osteogenesis of MC3T3 cells.