Chitosan Nanogel with Mixed Food Plants and Its Relation to Blood Glucose in Type 2 Diabetes: A Systematic and Meta-Analysis Review of Observational Studies

This systematic review with metanalysis evaluated and analyzed the beneficial effects of certain plants food in type 2 diabetes (T2D) when consumed alone or in combination with chitosan. The main objective of the paper was to examine the relation of chitosan nanogel and mixed food plant (MFP) to control T2D. The databases included Medline, Scopus, PubMed, as well as Cochrane available between the month of January 1990 to January 2021. The eligibility criteria for selecting studies were case-controlled studies that included unripe plantain, bitter yam, okra, and chitosan either used-alone or in combination with non-specified food plants (NSFP). Two-fold autonomous critics retrieved the information required and evaluated the risk of bias of involved studies. Random-effect meta-analyses on blood glucose controls, were performed. Results of 18 studies included: seven that examined unripe plantains, one bitter yam, two okras, and eight chitosan, found regarding the decrease in blood glucose level. Meta-analysis of the results found a large proportion of I2 values for all studies (98%), meaning heterogeneity. As a consequence, the combined effect sizes were not useful. Instead, prediction interval (PI) was used (mean difference 4.4 mg/dL, 95% PI −6.65 to 15.50 and mean difference 3.4 mg/dL, 95% PI −23.65 to 30.50) rather than the estimate of its confidence interval (CI). These studies were at 50% high risk of bias and 50% low risk of bias and there was judged to be an unclear risk of bias due to the insufficient information from the included study protocol (moderately low). The intervention lasted between three and 84 days, indicating potency and effectiveness of the intervention at both short and long durations. Due to the moderately low quality of the studies, the findings were cautiously interpreted. In conclusion, the current evidence available from the study does support the relation of chitosan with mixed unripe plantain, bitter yam and okra for the management of T2D. Further high-quality case-controlled animal studies are required to substantiate if indeed chitosan nanogel should be cross-linked with the specified food plant (SFP) for the management T2D

Correction: cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways

Background: Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development. Methods: In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters. Results: Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Specifically, gene expression analysis demonstrated that at day 0 the RAS system is involved. This is altered at day 6, when Wnt signaling and focal adhesion pathways are affected. However, at and after 24 days, proliferation, apoptosis, altered ECM signaling and many other factors become involved. Conclusions: Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation

Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2

<p>Abstract</p> <p>Background</p> <p>Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genes <it>PKD1 </it>and <it>PKD2 </it>account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product of <it>PKD2</it>. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2.</p> <p>Methods</p> <p>Here we utilized different kidney cell-lines expressing wild-type and mutant <it>PKD2 </it>as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.</p> <p>Results</p> <p>Surprisingly, over-expression of wild-type <it>PKD2 </it>in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutated <it>PKD2 </it>augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57^KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels.</p> <p>Conclusion</p> <p>Our results indicate the probable involvement of p57^KIP2on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21.</p

Chitosan Nanogel with Mixed Food Plants and Its Relation to Blood Glucose in Type 2 Diabetes: A Systematic and Meta-Analysis Review of Observational Studies

This systematic review with metanalysis evaluated and analyzed the beneficial effects of certain plants food in type 2 diabetes (T2D) when consumed alone or in combination with chitosan. The main objective of the paper was to examine the relation of chitosan nanogel and mixed food plant (MFP) to control T2D. The databases included Medline, Scopus, PubMed, as well as Cochrane available between the month of January 1990 to January 2021. The eligibility criteria for selecting studies were case-controlled studies that included unripe plantain, bitter yam, okra, and chitosan either used-alone or in combination with non-specified food plants (NSFP). Two-fold autonomous critics retrieved the information required and evaluated the risk of bias of involved studies. Random-effect meta-analyses on blood glucose controls, were performed. Results of 18 studies included: seven that examined unripe plantains, one bitter yam, two okras, and eight chitosan, found regarding the decrease in blood glucose level. Meta-analysis of the results found a large proportion of I2 values for all studies (98%), meaning heterogeneity. As a consequence, the combined effect sizes were not useful. Instead, prediction interval (PI) was used (mean difference 4.4 mg/dL, 95% PI &minus;6.65 to 15.50 and mean difference 3.4 mg/dL, 95% PI &minus;23.65 to 30.50) rather than the estimate of its confidence interval (CI). These studies were at 50% high risk of bias and 50% low risk of bias and there was judged to be an unclear risk of bias due to the insufficient information from the included study protocol (moderately low). The intervention lasted between three and 84 days, indicating potency and effectiveness of the intervention at both short and long durations. Due to the moderately low quality of the studies, the findings were cautiously interpreted. In conclusion, the current evidence available from the study does support the relation of chitosan with mixed unripe plantain, bitter yam and okra for the management of T2D. Further high-quality case-controlled animal studies are required to substantiate if indeed chitosan nanogel should be cross-linked with the specified food plant (SFP) for the management T2D

A miR-1207-5p binding site polymorphism abolishes regulation of HBEGF and is associated with disease severity in CFHR5 nephropathy.

Heparin binding epidermal growth factor (HBEGF) is expressed in podocytes and was shown to play a role in glomerular physiology. MicroRNA binding sites on the 3'UTR of HBEGF were predicted using miRWalk algorithm and followed by DNA sequencing in 103 patients diagnosed with mild or severe glomerulopathy. A single nucleotide polymorphism, miRSNP C1936T (rs13385), was identified at the 3'UTR of HBEGF that corresponds to the second base of the hsa-miR-1207-5p seed region. When AB8/13 undifferentiated podocytes were transfected with miRNA mimics of hsa-miR-1207-5p, the HBEGF protein levels were reduced by about 50%. A DNA fragment containing the miRSNP allele-1936C was cloned into the pMIR-Report Luciferase vector and co-transfected with miRNA mimics of hsa-miR-1207-5p into AB8/13 podocytes. In agreement with western blot data, this resulted in reduced luciferase expression demonstrating the ability of hsa-miR-1207-5p to directly regulate HBEGF expression. On the contrary, in the presence of the miRSNP 1936T allele, this regulation was abolished. Collectively, these results demonstrate that variant 1936T of this miRSNP prevents hsa-miR-1207-5p from down-regulating HBEGF in podocytes. We hypothesized that this variant has a functional role as a genetic modifier. To this end, we showed that in a cohort of 78 patients diagnosed with CFHR5 nephropathy (also known as C3-glomerulopathy), inheritance of miRSNP 1936T allele was significantly increased in the group demonstrating progression to chronic renal failure on long follow-up. No similar association was detected in a cohort of patients with thin basement membrane nephropathy. This is the first report associating a miRSNP as genetic modifier to a monogenic renal disorder

Mildly affected CFHR5 patients have lower occurrence of the 1936T allele.

<p>Graphical representation of both TBMN and CFHR5 nephropathy cohorts used in this study in relation to the number of CT and TT patients. Nephropathy patients with mild CFHR5 have significantly lower percentage of the CT genotype when compared with severe CFHR5 patients (p = 0.018), indicating a protective effect of the CC genotype. Statistical comparison between mild TBMN and mild CFHR5 patients demonstrated a significant underrepresentation of the 1936T allele in mild CFHR5 patients (p = 0.038). Mild TBMN patients did not differ from severe TBMN patients (p = 0.368). All statistical analyses were performed using two-sided Barnard's test.</p

Expression analysis of miR-1207-5p in various cell lines.

<p>Relative expression analysis of mature hsa-miR-1207-5p levels in various cell types, as tested by miRNA specific Real-Time PCR experiments. Both AB8/13 differentiated and undifferentiated podocytes revealed significantly high expression levels of miR-1207-5p, compared to HEK293 and SHSY-5Y neuroblastoma cells. Further examination of miR-1207-5p levels in human renal epithelial cells (HREpiC), recorded 4-fold higher mature miRNA than the AB8/13 differentiated podocyte cell line. Results represent the mean of quadruplicate values ± SEM.</p