Recent advances in pH-sensitive indicator films based on natural colorants for smart monitoring of food freshness: a review.

As a new type of packaging method, natural pigment-based pH-sensitive indicator film packaging can be used to intelligently monitor food freshness, provide consumers with intuitive food freshness information, and own the advantages of small size, low cost and intuitive accuracy. Based on the introduction of the principle of natural pigment in pH-sensitive indicator film intelligent packaging, this paper reviews the types of natural pigment indicators (such as anthocyanins, curcumin) and film-forming matrix materials, and systematically discusses the research progress of their application in freshness monitoring in various foods, and points out the limitations of this intelligent packaging in practical applications. In order to provide natural pigment in the application and promotion of pH-sensitive indicator film packaging for monitoring food freshness, further research and development works are required to overcome the current limitations. The needs for further research and developments are outlined.

Risk factors for hypocalcemia in dialysis patients with refractory secondary hyperparathyroidism after parathyroidectomy: a meta-analysis.

OBJECTIVE: Hypocalcemia after parathyroidectomy (PTX) results in tetany, diarrhea, cardiac arrhythmia, and even sudden death. However, a meta-analysis or systematic evaluation of risk factors with the occurrence and development of hypocalcemia in patients with secondary hyperparathyroidism (SHPT) after PTX has never been performed. METHODS: A thorough search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE, was performed to retrieve relevant studies from database inception to June 2021. Quality of the included studies was assessed by two independent reviewers using the Newcastle-Ottawa Scale. Review Manager 5.3 and Stata 16.0 were used for meta-analysis. The random-effects model was adopted to calculate the 95% CIs (I2> 50% or p < 0.05) of the combined effect size and the corresponding homogeneous data. Otherwise, a fixed-effects model was used. RESULTS: Thirteen studies including 2990 participants who met the inclusion criteria were enrolled in the present meta-analysis. The overall quality of the enrolled studies had a score of >7 points. Risk factors significantly related to hypocalcemia in patients with SHPT after PTX were preoperative serum calcium (OR 0.19, 95%CI 0.11-0.31), preoperative alkaline phosphatase (ALP) (OR 1.01, 95% CI 1.01-1.02), and preoperative intact parathyroid hormone (iPTH) (OR 1.38, 95%CI 1.20-1.58). Meanwhile, age (OR 0.97, 95%CI 0.87-1.10) was not significantly correlated with hypocalcemia after PTX. CONCLUSIONS: Based on the current evidence, preoperative serum calcium, preoperative ALP, and preoperative iPTH were significant predictors of hypocalcemia in patients with SHPT after PTX. More attention should be given to patients with these risk factors for the prevention of postoperative hypocalcemia.

Serum elabela and apelin levels during different stages of chronic kidney disease.

PURPOSE: The association of serum elabela (ELA) and apelin with the progression of chronic kidney disease (CKD) is unknown. We determined if serum ELA and apelin levels were associated with CKD stage. METHODS: This observational study involved 60 CKD patients and 20 healthy, age-, race-, and gender-matched controls. The participants were grouped according to renal function as follows: normal control group, CKD1 group (stage-1 CKD, 20 patients), CKD3 group (stage-3 CKD, 20 patients), and CKD5 group (stage-5 CKD, 20 patients) in accordance with the Kidney Disease Outcomes - Quality Initiative criteria. We recorded the demographic, clinical, and biochemical data of all participants. Serum ELA and apelin levels were measured using commercially available enzyme-linked immunosorbent assays. RESULTS: Serum ELA levels gradually and significantly declined with decreases in the estimated glomerular filtration rate (eGFR). Serum ELA showed significant negative correlations with serum creatinine (r = -0.529, p < .001), blood urea nitrogen (r = -0.575, p < .001), systolic blood pressure (r = -0.455, p < .001), and diastolic blood pressure (r = -0.450, p < .001), and significant positive correlations with hemoglobin (r = 0.523, p < .001) and eGFR (r = 0.728, p < .001). Multiple regression analysis showed that eGFR independently influenced serum ELA levels. No significant association was found between serum apelin levels and CKD progression. CONCLUSION: In CKD patients, serum ELA levels decreased with decreasing eGFR. This finding may provide a new target for the prediction, diagnosis, and staging of CKD.

Emerging frontiers in drug delivery with special focus on novel techniques for targeted therapies.

The management and treatment of disease are achieved via the use of pharmacologically active substances or drugs. Drugs do not, however, have an intrinsic ability to be effective; rather, how well they work depends on how they are administered or supplied. Treatment of a variety of biological illnesses, such as autoimmune disorders, cancer, and bacterial infections, requires effective drug delivery. Drug absorption, distribution, metabolism, duration of therapeutic impact, pharmacokinetics, excretion, and toxicity can all be impacted by drug administration. Improved chemistry and materials are required for the delivery of therapeutic concentration of novel treatments to the specified targets within the body, as well as for the necessary duration of time. This requirement is accompanied by the development of new therapeutics. Formulating a medication as a DDS is a promising strategy for directly addressing numerous typical barriers to adherence, such as frequent dosage, such as frequent dosage, side effects, and a delayed beginning of the action. In the current review, we give a compendium of drug delivery and controlled release and subsequently highlight some of the newest developments in the realm, with a particular emphasis on cutting-edge methods for targeted therapy. In each instance, we outline the obstacles to efficient drug administration as well as the chemical and material developments that are allowing the sector to overcome these obstacles and have a positive clinical impact.

Multidrug-resistant organism-peritoneal dialysis associated peritonitis: clinical and microbiological features and risk factors of treatment failure.

Background: Multidrug-resistant (MDR) bacterial infection causes difficulty in the therapy of peritoneal dialysis-associated peritonitis (PDAP); however, there are few studies on multidrug-resistant organism (MDRO)-PDAP. In view of growing concerns about MDRO-PDAP, the aim of this study was to investigate the clinical features, risk factors of treatment failure, and causative pathogens of MDRO-PDAP. Methods: In total, 318 patients who underwent PD between 2013 and 2019 were included in this multicenter retrospective study. Clinical features, patient outcomes, factors related to treatment failure, and microbiological profiles associated with MDRO-PDAP were analyzed and risk factors for treatment failure associated with MDR-Escherichia coli (E. coli) were further discussed. Results: Of 1,155 peritonitis episodes, 146 eligible episodes of MDRO-PDAP, which occurred in 87 patients, were screened. There was no significant difference in the composition ratio of MDRO-PDAP between 2013-2016 and 2017-2019 (p > 0.05). E. coli was the most prevalent MDRO-PDAP isolate, with high sensitivity to meropenem (96.0%) and piperacillin/tazobactam (89.1%). Staphylococcus aureus was the second most common isolate and was susceptible to vancomycin (100%) and linezolid (100%). Compared to non-multidrug-resistant organism-PDAP, MDRO-PDAP was associated with a lower cure rate (66.4% vs. 85.5%), higher relapse rate (16.4% vs. 8.0%), and higher treatment failure rate (17.1% vs.6.5%). Dialysis age [odds ratio (OR): 1.034, 95% confidence interval (CI): 1.016-1.052, p < 0.001] and >2 previous peritonitis episodes (OR: 3.400, 95% CI: 1.014-11.400, p = 0.047) were independently associated with treatment failure. Furthermore, longer dialysis age (OR: 1.033, 95% CI: 1.003-1.064, p = 0.031) and lower blood albumin level (OR: 0.834, 95% CI: 0.700-0.993, p = 0.041) increased the risk of therapeutic failure for MDR-E. coli infection. Conclusion: The proportion of MDRO-PDAP has remained high in recent years. MDRO infection is more likely to result in worse outcomes. Dialysis age and previous multiple peritonitis infections were significantly associated with treatment failure. Treatment should be promptly individualized based on local empirical antibiotic and drug sensitivity analyses.

12-Lipoxygenase as a key pharmacological target in the pathogenesis of diabetic nephropathy.

The characteristic features of diabetic nephropathy include thickening of the glomerular basement membranes, expansion of mesangium, and appearance of albumin in the urine (microalbuminuria and macroalbuminuria). Experimental studies have documented that 12-lipoxygenase (12-LOX) and its metabolite 12(S)-hydroxyeicosatetraenoic acid (HETE) play an important role in the pathogenesis of diabetic nephropathy. 12(S)-HETE may work in association with angiotensin II and transforming growth factor- ß (TGF-ß) reciprocally to induce fibrotic changes in the diabetic kidneys. The fibrotic actions of angiotensin II on the kidneys are mediated indirectly through an increase in the synthesis of 12(S)-HETE. Conversely, 12(S)-HETE may also enhance the actions of angiotensin II by upregulating the expression of AT1 receptors on the glomerulus, mesangium, and podocytes. 12(S)-HETE may also cross-talk with TGF-ß in a reciprocal manner to induce the fibrotic changes in the diabetic kidney. 12(S)-HETE-triggered signaling pathways may involve activation of p38 mitogen-activated protein (p38MAP) kinase, increase in cAMP-responsive element-binding protein (CREB) transcriptional activity, epigenetic changes involving histone methylation through an increase in histone methyltransferase activity along with an upregulation of cyclin-kinase inhibitors including, p16, p21, and p27. The present review discusses the role of 12-LOX in the pathogenesis of diabetic nephropathy along with the possible mechanisms.

Serum lncRNA HAND2-AS1 is downregulated in diabetic patients with chronic renal failure and ameliorates cell apoptosis.

BACKGROUND: LncRNA HAND2-AS1 has been reported to be a tumor suppressor in several types of malignancy, while its involvement in other human diseases is unclear. Our preliminary RNA-seq analysis revealed the downregulation of lncRNA HAND2-AS1 in diabetic patients with chronic renal failure, indicating the involvement of lncRNA HAND2-AS1 in this disease. This study was therefore carried out to explore the role of lncRNA HAND2-AS1 in the development of chronic renal failure in diabetic patients. METHODS: Mouse podocyte cells and plasma samples of diabetic patients (46 diabetic patients with chronic renal failure, 38 diabetic patients without obvious complications and 42 healthy volunteers) were used in this study. Cell apoptosis assay and PCR were performed. RESULTS: LncRNA HAND2-AS1 was downregulated in diabetic patients with chronic renal failure but not in diabetic patients without obvious complications. Downregulation of lncRNA HAND2-AS1 distinguished diabetic patients with chronic renal failure from diabetic patients and healthy controls. High glucose environment did not affect the expression of lncRNA HAND2-AS1 in mouse podocyte cells. Overexpression of lncRNA HAND2-AS1 inhibited the apoptosis of mouse podocyte cells under high glucose treatment. CONCLUSIONS: We therefore conclude that lncRNA HAND2-AS1 may participate in the development of chronic renal failure in diabetic patients by regulating cell apoptosis.

Application of automated peritoneal dialysis in urgent-start peritoneal dialysis patients during the break-in period.

OBJECTIVE: Whether automated peritoneal dialysis (APD) is a feasible strategy for urgent-start peritoneal dialysis (PD) therapy during the break-in period remains unclear. This study was conducted to compare the efficacy as well as complications among three PD modes during the break-in period. METHODS: Ninety-six patients treated with urgent-start PD after catheterization were retrospectively analyzed. Patients were divided into three groups, incremental continuous ambulatory PD (CAPD) group (n = 26); APD group (n = 42); and APD-CAPD group (n = 28). Clinical parameters at the end of the break-in period and 1 month after the initiation of PD treatment were collected and analyzed. RESULTS: Compared with the traditional incremental CAPD, APD and APD-CAPD were superior as they could effectively remove small-molecule uremic toxins and correct electrolyte imbalance (P < 0.05), while did not increase the incidence of early complications during the break-in period (P > 0.05). However, APD led to a significant decline in albumin and pre-albumin, as compared with APD-CAPD and CAPD (P < 0.05). A PD strategy consisting 6 days of APD and 3 days of CAPD showed a great advantage in preventing excessive protein loss. There were no significant differences in all tested biochemical parameters among the three groups at 1 month after treatment (all P > 0.05). CONCLUSION: Application of APD for urgent-start PD during the break-in period is feasible. A combination of APD and CAPD regimens seems to be a more reasonable mode.

Hologenomic adaptations underlying the evolution of sanguivory in the common vampire bat.

Adaptation to specialized diets often requires modifications at both genomic and microbiome levels. We applied a hologenomic approach to the common vampire bat (Desmodus rotundus), one of the only three obligate blood-feeding (sanguivorous) mammals, to study the evolution of its complex dietary adaptation. Specifically, we assembled its high-quality reference genome (scaffold N50 = 26.9 Mb, contig N50 = 36.6 kb) and gut metagenome, and compared them against those of insectivorous, frugivorous and carnivorous bats. Our analyses showed a particular common vampire bat genomic landscape regarding integrated viral elements, a dietary and phylogenetic influence on gut microbiome taxonomic and functional profiles, and that both genetic elements harbour key traits related to the nutritional (for example, vitamin and lipid shortage) and non-nutritional (for example, nitrogen waste and osmotic homeostasis) challenges of sanguivory. These findings highlight the value of a holistic study of both the host and its microbiota when attempting to decipher adaptations underlying radical dietary lifestyles.

Identification of potential biomarkers and therapeutic targets for human IgA nephropathy and hypertensive nephropathy by bioinformatics analysis.

In order to further elucidate the potential correlations and treatments of IgA nephropathy (IgAN) and hypertensive nephropathy (HT), bioinformatics analysis of IgAN and HT was performed. The mRNA expression profiles of human renal biopsy samples from patients with IgAN, patients with HT and pre­transplant healthy living controls (LD) were downloaded from the Gene Expression Omnibus database. Then, the differentially expressed genes (DEGs) were identified and functions of DEGs were analyzed. Finally, the regulatory networks containing DEGs and related­transcription factors (TFs) were constructed using Cytoscape software. When compared with the LD group, 134 and 188 DEGs were obtained in the IgAN and HT groups, respectively. A total of 39 genes were altered in the HT group when compared with the IgAN group. In addition, 66 genes were shared in the IgAN and HT groups when compared with the LD group, 6 of which [early growth response 1, activating transcription factor 3, nuclear receptor subfamily 4 group A member 2 (NR4A2), NR4A1, v­maf avian musculoaponeurotic fibrosarcoma oncogene homolog F and Kruppel like factor 6] were identified as TFs. In addition, DEGs including interleukin (IL) 1 receptor antagonist, collagen type 4 α2 chain, IL8, FBJ murine osteosarcoma viral oncogene homolog and somatostatin were enriched in a number of inflammation­associated biological processes, and DEGs including structural maintenance of chromosomes protein 3, v­crk avian sarcoma virus CT10 oncogene homolog and myosin 6 were enriched in non­inflammation­associated biological processes. Therefore, the differentially expressed TF genes and the genes associated with inflammation may be effective as potential therapeutic targets for IgAN and HT.

Role of Smad signaling in kidney disease.

Smads are the key intermediates of canonical transforming growth factor-beta (TGF-ß) signaling. These intermediates are divided into three distinct subgroups based on their role in TGF-ß family signal transduction: Receptor-regulated Smads (R-Smads) 1, 2, 3, 5 and 8, common Smad4, and inhibitory Smads6 and 7. TGF-ß signaling through Smad pathway involves phosphorylation, ubiquitination, sumoylation, acetylation, and protein-protein interactions with mitogen-activated protein kinases, PI3K-Akt/PKB, and Wnt/GSK-3. Several studies have suggested that upregulation or downregulation of TGF-ß/Smad signaling pathways may be a pathogenic mechanism in the progression of chronic kidney disease. Smad2 and 3 are the two major downstream R-Smads in TGF-ß-mediated renal fibrosis, while Smad7 also controls renal inflammation. In this review, we characterize the role of Smads in kidney disease, describe the molecular mechanisms, and discuss the potential of Smads as a therapeutic target in chronic kidney disease.

Association between glucose transporter 1 rs841853 polymorphism and type 2 diabetes mellitus risk may be population specific (1rs8418532).

BACKGROUND: So far, studies on the association between the glucose transporter 1 (GLUT1) rs841853 polymorphism and type 2 diabetes mellitus (T2DM) risk have generated considerable controversy. The present study was performed to clarify the association of this genetic variation with T2DM. METHODS: A comprehensive literature search of electronic databases was conducted to obtain articles focused on the relationship between the GLUT1 rs841853 polymorphism and T2DM, followed by a systemic meta-analysis. RESULTS: Fourteen articles and 19 individual studies were included for analysis. Main analyses revealed extreme heterogeneity and random effect pooled odds ratios (OR) were weakly significant in allele contrast (OR 1.28; 95% confidence interval [CI] 1.01, 1.63; P=0.04) and dominant model (OR 1.52; 95% CI 1.19, 1.94; P=0.0008) for T allele. Subgroup analyses for Caucasians showed marginal positive results in the dominant model. However, analyses for Asians yielded an obvious relationship to T2DM risk in all genetic models. Interestingly, T allele even seemed to be a protective factor against the development of T2DM in Blacks in allele contrast. Sensitivity analyses did not alter materially for most comparisons and no publication bias was found in this meta-analysis. CONCLUSIONS: The results of the present meta-analysis provide evidence that the GLUT1 rs841853 polymorphism may confer increased susceptibility to T2DM in Asians. However, there is no currently available strong evidence supporting the association between this genetic variation and T2DM in Caucasians, Blacks, or the overall population.

Is C677T polymorphism in methylenetetrahydrofolate reductase gene a risk factor for diabetic nephropathy or diabetes mellitus in a Chinese population?

BACKGROUND AND AIMS: To date, case-control studies on the association between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene and diabetes mellitus (DM) or diabetic nephropathy (DN) in different populations have provided inconclusive results. To clarify the effect of the C677T polymorphism on the risk of both DM and DN in a Chinese population, a meta-analysis was performed. METHODS: A comprehensive literature search was conducted to collect data from all case-control observational studies that investigated association of C677T polymorphism in MTHFR gene with DM or DN in a Chinese population. RESULTS: Overall, 12 studies in a Chinese population published up to 2011 were combined, and the heterogeneity among them varied from none to moderate. The 677T allele showed significant association with DN (OR = 1.97, 95% CI [1.71, 2.28], p <0.00001), but no relationship with DM (OR = 1.03, 95% CI [0.89, 1.18], p = 0.70) compared with the 677C allele in a Chinese population. Similarly, evidence of significant association with DN was detected in the additive model, the recessive model and the dominant model for allele T (additive model: OR = 3.26, 95% CI [2.46, 4.31], p <0.00001; recessive model: OR = 2.32, 95% CI [1.81, 2.97], p <0.00001; dominant model: OR = 2.35, 95% CI [1.89, 2.91], p <0.00001); however, no relationship with DM was found (additive model: OR = 1.01, 95% CI [0.76, 1.35], p = 0.94; recessive model: OR = 0.98, 95% CI [0.76, 1.26], p = 0.87; dominant model: OR = 1.23, 95% CI [0.91, 1.65], p = 0.18). There were no sources of bias in the selected studies, and the sensitivity analysis (exclusion of studies not in Hardy-Weinberg equilibrium) suggested stability of this meta-analysis. CONCLUSIONS: C677T polymorphism in MTHFR gene may be a risk factor for DN, but not for DM, in a Chinese population.