Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice.

Chemoresistance and chemotherapy-related ovarian damage are well-reported in breast cancer (BC) young patients. Herein, the inhibition of the mitochondrial fission was invested to explore its chemosensitizing role in Paclitaxel (PTX)-resistant cells, and its ability to restore the ovarian integrity in mice receiving PTX or cisplatin chemotherapy. To establish these aims, PTX-resistance was generated in BC cells, which were treated with PTX in combination with Drp1 deficiency, via mdivi-1, or Drp1-specific siRNA transfection. Furthermore, the alterations in the ovarian structure and the endocrine-related hormones were explored in mice receiving repetitive doses of PTX or cisplatin. We found that combining PTX with mdivi-1 improved cell responsiveness to PTX, induced apoptosis- and autophagy-mediated cell death, and relieved cellular oxidative stress. Additionally, the expression of PCNA1 and cyclin B1 genes were downregulated, meanwhile, p53, p21, and mitochondrial fusion proteins (Mfu1&Mfu2) were increased. The in vivo investigations in mice demonstrated that PTX induced gonadotoxic damage similar to cisplatin, whereas dual treatment of mice with PTX+ mdivi-1 failed to restore their normal follicular count and the circulating levels of E2 and AMH hormones. These results suggested that combining Drp1 inhibition with PTX resensitized breast cancer cells to PTX but failed to offer enough protection against chemotherapy-related gonadotoxicity.

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility.

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.

Fabrication of bioactive nanocomposites from chitosan, cress mucilage, and selenium nanoparticles with powerful antibacterial and anticancerous actions.

Natural bioactive alternatives are the utmost requests from researchers to provide biosafe and effectual health-guarding agents. The biopolymers chitosan nanoparticles (NCT), mucilage of cress seed (GCm; Lepidium sativum), and GCm-mediated selenium nanoparticles (GCm/SeNPs) were innovatively employed for fabricating novel bioactive natural nanocomposites (NCs) with elevated bioactivities as bactericidal (against Salmonella typhimurium and Staphylococcus aureus) and anticancer (against CaCo-2 and HeLa cells). The SeNPs were successfully generated with GCm, and different NCs formulations were fabricated from NCT:GCm/SeNPs amalgam ratios including T1, T2, and T3 with 2:1, 1:1, and 1:2 ratios, respectively. The infrared analysis of synthesized molecules appointed apparent physical interactions among interacted molecules. The average particles' sizes and charges of molecules/NCs were (12.7, 316.4, 252.8, and 127.3 nm) and (-6.9, +38.7, +26.2, and -25.8 mV) for SeNPs, T1, T2, and T3, respectively. The biocidal assessment of NCs indicated that T1 was the strongest antibacterial formulation, whereas T3 was the superior anticancer amalgam. These NCs formulations could exceed the biocidal potentialities of standard biocides. T1-NC could cause severe destructions/deformations in challenged S. typhimurium within 9 h, whereas T3-NCs induced apparent fluorescent apoptosis signs in treated HeLa cells. The prospective applications innovatively designed biocidal natural NCs that are recommended for controlling pathogenic bacteria and fighting cancerous cells.

Corrigendum: Foliar application of putrescine alleviates terminal drought stress by modulating water status, membrane stability, and yield- related traits in wheat (Triticum aestivum L.).

[This corrects the article DOI: 10.3389/fpls.2022.1000877.].

Facile Synthesis, Characterization, and Antimicrobial Assessment of a Silver/Montmorillonite Nanocomposite as an Effective Antiseptic against Foodborne Pathogens for Promising Food Protection.

Foodborne pathogens can have devastating repercussions and significantly threaten public health. Therefore, it is indeed essential to guarantee the sustainability of our food production. Food preservation and storage using nanocomposites is a promising strategy. Accordingly, the present research's objectives were to identify and isolate a few foodborne pathogens from food products, (ii) synthesize and characterize silver nanoparticles (AgNPs) using wet chemical reduction into the lamellar space layer of montmorillonite (MMT), and (iii) investigate the antibacterial potential of the AgNPs/MMT nanocomposite versus isolated strains of bacteria. Six bacterial species, including Escherichia coli, Salmonella spp., Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus were isolated from some food products (meat, fish, cheese, and vegetables). The Ag/MMT nanocomposite was synthesized and characterized using UV-visible spectroscopy, transmission electron microscopy, particle size analyzer, zeta potential, X-ray diffraction (XRD), and scanning electron microscopy with dispersive energy X-ray (EDX). The antibacterial effectiveness of the AgNPs/MMT nanocomposite further investigated distinct bacterial species using a zone of inhibition assay and microtiter-based methods. Nanoparticles with a narrow dimension range of 12 to 30 nm were identified using TEM analysis. The SEM was employed to view the sizeable flakes of the AgNPs/MMT. At 416 nm, the most excellent UV absorption was measured. Four silver metallic diffraction peaks were found in the XRD pattern during the study, and the EDX spectrum revealed a strong signal attributed to Ag nanocrystals. AgNPs/MMT figured out the powerful antibacterial action. The AgNPs/MMT nanocomposite confirmed outstanding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against six isolates of foodborne pathogens, ranging from 15 to 75 µg/mL, respectively. The AgNPs/MMT's antibacterial potential against gram-negative bacteria was noticeably better than gram-positive bacteria. Therefore, the AgNPs/MMT nanocomposite has the potential to be used as a reliable deactivator in food processing and preservation to protect against foodborne pathogenic bacteria. This suggests that the nanocomposite may be effective at inhibiting the growth and proliferation of harmful bacteria in food, which could help to reduce the risk of foodborne illness.

Preparation of afterglow and photochromic fibrous mats from polypropylene plastics to detect ultraviolet light.

Polypropylene textiles have been used in the development of various industrial products, such as automotives, plastic furniture, and medical tools. However, polypropylene resists dyeing due to a deficiency of active staining spots. Here, we developed a new strategy towards new afterglow and photochromic fibres from recycled polypropylene plastics using plasma-supported coloration with rare-earth activated aluminate nanoparticles (REANPs). Plasma curing was used to generate active dyeing sites on the polypropylene surface. A thin film of REANPs (2-10 nm) was deposited onto the plasma-pretreated polypropylene surface. Various analytical techniques were applied to inspect the morphology of the REANP-finished polypropylene fibres. The polypropylene dyeing activity was much improved after being exposed to plasma. Both photoluminescence analysis and Commission internationale de l'éclairage (CIE) laboratory coordinates proved that the polypropylene fibres exhibited a white colour in daylight and green in ultraviolet light. The thin afterglow layer immobilized onto the polypropylene surface exhibited an emission band of 524 nm upon excitation at 365 nm. The sliding angles dropped from 12° to 9°, but the contacting angles increased from 139.4° to 145.0° when the REANP ratio was raised. These findings show that REANP-finished polypropylene had good colourfastness, antimicrobial activity, and ultraviolet light blocking. Both stiffness and permeability to air of REANP-finished polypropylene were explored to designate excellent comfort characteristics.

Maximizing the energy recovery from rice straw through two-step conversion using eggshell-catalytic pyrolysis followed by enhanced anaerobic digestion using calcium-rich biochar.

Anaerobic digestion of lignocelluloses for biogas production is greatly restricted by the poor biomass degradability. Herein, a novel approach is suggested to enhance the energy recovery from rice straw through a two-step conversion using eggshell-based catalytic pyrolysis followed by biochar-based anaerobic co-digestion. Pyrolysis with eggshell significantly enhanced the crude bio-oil yield by 4.6 %. Anaerobic digestion of rice straw using 4 g L-1 of rice straw biochar (RB) showed the highest recorded biogas yield of 503.7 L kg-1 VS, with 268.6 L kg-1 VS biomethane yield. However, 4 g L-1 of calcium-enriched eggshell rice straw biochar (ERB) enhanced the biomethane yield to 281.8 L kg-1 VS, which represented 95.6 % higher than the control. It was attributed to enhancement of biomethanation, which resulted in 74.5 % maximum recorded biomethane content at the 7th day of anaerobic digestion. Microbial analysis confirmed that Methanosarciniales was the most dominant Archael group in the control (14.84 %), which increased sharply to 73.91 % and 91.66 % after addition of 4 g L-1 RB and ERB, respectively. The suggested route enhanced the energy recovery in the form of bio-oil and biomethane by 41.6 %.

Fabrication and assessment of potent anticancer nanoconjugates from chitosan nanoparticles, curcumin, and eugenol.

In cancer management and control, the most challenging difficulties are the complications resulting from customized therapies. The constitution of bioactive anticancer nanoconjugates from natural derivatives, e.g., chitosan (Ct), curcumin (Cur), and eugenol (Eug), was investigated for potential alternatives to cancer cells' treatment. Ct was extracted from Erugosquilla massavensis (mantis shrimp); then, Ct nanoparticles (NCt) was fabricated and loaded with Cur and/or Eug using crosslinking emulsion/ionic-gelation protocol and evaluated as anticancer composites against CaCo2 "colorectal adenocarcinoma" and MCF7 "breast adenocarcinoma" cells. Ct had 42.6 kDa molecular weight and 90.7% deacetylation percentage. The conjugation of fabricated molecules/composites and their interactions were validated via infrared analysis. The generated nanoparticles (NCt, NCt/Cur, NCt/Eug, and NCt/Cur/Eug composites) had mean particle size diameters of 268.5, 314.9, 296.4, and 364.7 nm, respectively; the entire nanoparticles carried positive charges nearby ≥30 mV. The scanning imaging of synthesized nanoconjugates (NCt/Cur, NCt/Eug, and NCt/Cur/Eug) emphasized their homogenous distributions and spherical shapes. The cytotoxic assessments of composited nanoconjugates using the MTT assay, toward CaCo2 and MCF7 cells, revealed elevated anti-proliferative and dose-dependent activities of all nanocomposites against treated cells. The combined nanocomposites (NCt/Eug/Cur) emphasized the highest activity against CaCo2 cells (IC50 = 11.13 µg/ml), followed by Cur/Eug then NCt/Cur. The exposure of CaCo2 cells to the nanocomposites exhibited serious DNA damages and fragmentation in exposed cancerous cells using the comet assay; the NCt/Eug/Cur nanocomposite was the most forceful with 9.54 nm tail length and 77.94 tail moment. The anticancer effectuality of innovatively combined NCt/Cur/Eug nanocomposites is greatly recommended for such biosafe, natural, biocompatible, and powerful anticancer materials, especially for combating colorectal adenocarcinoma cells, with elevated applicability, efficiency, and biosafety.

Fabrication of Nanofibers Based on Hydroxypropyl Starch/Polyurethane Loaded with the Biosynthesized Silver Nanoparticles for the Treatment of Pathogenic Microbes in Wounds.

Fabrication of electrospun nanofibers based on the blending of modified natural polymer, hydroxyl propyl starch (HPS) as one of the most renewable resources, with synthetic polymers, such as polyurethane (PU) is of great potential for biomedical applications. The as-prepared nanofibers were used as antimicrobial sheets via blending with biosynthesized silver nanoparticles (AgNPs), which were prepared in a safe way with low cost using the extract of Nerium oleander leaves, which acted as a reducing and stabilizing agent as well. The biosynthesized AgNPs were fully characterized by various techniques (UV-vis, TEM, DLS, zeta potential and XRD). The obtained results from UV-vis depicted that the AgNPs appeared at a wavelength equal to 404 nm affirming the preparation of AgNPs when compared with the wavelength of extract (there are no observable peaks). The average particle size of the fabricated AgNPs that mediated with HPS exhibited a very small size (less than 5 nm) with excellent stability (more than -30 mv). In addition, the fabricated nanofibers were also fully characterized and the obtained data proved that the diameter of nanofibers was enlarged with increasing the concentration of AgNPs. Additionally, the findings illustrated that the pore sizes of electrospun sheets were in the range of 75 to 350 nm. The obtained results proved that the presence of HPS displayed a vital role in decreasing the contact angle of PU nanofibers and thus, increased the hydrophilicity of the net nanofibers. It is worthy to mention that the prepared nanofibers incorporated with AgNPs exhibited incredible antimicrobial activity against pathogenic microbes that actually presented in human wounds. Moreover, P. aeruginosa was the most sensitive species to the fabricated nanofibers compared to other tested ones. The minimal inhibitory concentrations (MICs) values of AgNPs-3@NFs against P. aeruginosa, and E. faecalis, were 250 and 500 mg/L within 15 min, respectively.

Foliar application of putrescine alleviates terminal drought stress by modulating water status, membrane stability, and yield- related traits in wheat (Triticum aestivum L.).

Drought stress is one of the major limitations to the growth and yield productivity of cereal crops. It severely impairs the early growing and grain -filling stages of wheat. Therefore, cost- effective and eco-friendly approaches for alleviating drought stress in cereal crops are in high demand. Polyamines, such as putrescine, have a significant effect on improving crop yield under drought- stress conditions. Therefore, the current study was executed with the aim of exploring the significance of putrescine in alleviating drought stress and improving yield- related traits in wheat. Two distinct wheat cultivars (Fakhar-e-Bhakkar and Anaj-2017) were treated with the foliar application of different concentrations (control, 0.5, 1.0, and 1.5 PPM) of putrescine (put) under two moisture conditions (well- watered and terminal drought stress). The results demonstrate that the imposition of terminal drought stress significantly reduces different physiological and yield- related traits of both wheat cultivars. The reduction of relative water content (RWC%), membrane stability index (MSI), leaf area, tillers per plant, biomass yield, number of spikelets per spike, 100-grain weight, grain yield per plant, and straw yield was greater in Anaj-2017 than in Fakhar-e-Bhakkar cultivar. The results further explain that the foliar application of increased concentrations of putrescine from 0.0 to 1.0 PPM gradually improved physiological and yield traits, whereas these traits declined with the application of putrescine at the highest dose (1.5 PPM). The exogenous application of 1.0 PPM putrescine improved the relative water content (19.76%), specific leaf area (41.47%), and leaf area ratio (35.84%) compared with the controlled treatment. A higher grain yield (28.0 g plant-1) and 100-grain weight (3.8 g) were obtained with the foliar application of 1.0 PPM putrescine compared with controlled treatments. The findings of this study confirm the protective role of putrescine against terminal drought stress. It is therefore recommended to use putrescine at a concentration of 1.0 PPM, which could help alleviate terminal drought stress and attain better wheat yield.

Immobilization of Strontium Aluminate into Recycled Polycarbonate Plastics towards an Afterglow and Photochromic Smart Window.

A transparent smart window made of recycled polycarbonate plastic (PCP) waste was prepared and immobilized with strontium aluminate phosphor nanoparticles (SAPN). It has afterglow emission, super-hydrophobicity, durability, photostability, good mechanical properties, ultraviolet protection, and high optical transmittance. To create an afterglow emission polycarbonate smart window (SAPN@PCP), recycled polycarbonate waste was integrated with various concentrations of SAPN (15-52 nm). SAP micro-scale powder was made using the solid-state high temperature method. The SAP nanoparticles were produced using the top-down method. To create a colorless plastic bulk, recycled polycarbonate waste was inserted into a hot bath. This colorless plastic was thoroughly combined with SAPN and cast to create an afterglow luminous smart window. To investigate its photoluminescence properties, spectrum profiles of excitation and emission were measured. According to the luminescence parameters, the phosphorescent colorless polycarbonate plates displayed a change in color to strong green under UV illumination and greenish-yellow in a dark box. The afterglow polycarbonate smart window displayed two emission peaks at 496 and 526 nm, and an absorption wavelength of 373 nm. Upon increasing the SAPN ratio, the hydrophobic activity, hardness, photostability, and UV protection were improved. Luminescent polycarbonate substrates with lower SAPN ratio demonstrated rapid and reversible fluorescence under UV light, while the higher SAPN content in the luminous polycarbonate substrates showed afterglow.

Association between IL-18 and IL-6 gene polymorphisms and the risk of T1D in Egyptian children.

PURPOSE: To test the involvement between IL-18 and IL-6 genetic polymorphisms and susceptibility to Type 1 diabetes (T1D). METHODS: Single nucleotide polymorphisms (SNPs) at positions -607A/C and - 137G/C in IL-18 promoter region were examined by sequence specific primers-polymerase chain reaction (SSP-PCR) and position -174G/C in promoter region of IL-6 gene which analyzed by Mutagenically Separated PCR (MS-PCR) in 104 T1D participants and 114 controls. RESULTS: IL-18 -137GC and -137CC genotypes and -137C allele were significantly decreased in T1D subjects (P < 0.05), while -137GG genotype was insignificantly increased as compared to controls. A significant decrease was detected in haplotype -137C/-607C frequency in T1D participants compared with controls (OR = 0.04, P < 0.001). There was significant association between IL-18 -607 of (CC, AC and AA genotypes) in age at diagnosis, glycated hemoglobin (HbA1c) and higher body mass index (BMI) (P < 0.05). CONCLUSION: This study demonstrated that IL-18 gene promoter polymorphisms might be associated with susceptibility to T1D in Egyptian children. Individuals carrying CC genotype at position -137 of IL-18 promoter may be at a low risk of T1D progression. Additionally, the susceptible combination of IL-18 and IL-6 cytokine genes associated with T1D highlight their risk toward the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00763-w.

Polyaspartate-Ionene/Na+-Montmorillonite Nanocomposites as Novel Adsorbent for Anionic Dye; Effect of Ionene Structure.

Surface modification of sodium montmorillonite (Na+-Mt) was performed using antimicrobial agents to produce an ecofriendly nanocomposite. The adsorption performance of the nanocomposite has been evaluated for the removal of Acid Blue 25 dye (AB25) as a model organic pollutant from wastewater. Sodium montmorillonite (Na+-Mt) was modified with three different ionene compounds through ion exchange, and further modified through reaction with polyaspartate to provide three ecofriendly nanocomposites (denoted ICP-1-3). The nanocomposites were characterized using FTIR, PXRD, TEM, SEM, and BET surface area. The adsorption isotherm of AB25 onto ICP-1, ICP-2 and ICP-3 was analyzed using the Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) models. The adsorption isotherm was found to be best fitted by a Freundlich model. The thermodynamic parameters were calculated. The kinetics of the adsorption data were analyzed and the adsorption behavior was found to obey pseudo-second-order kinetics, and the intraparticle diffusion model. The adsorption mechanism was studied by FTIR.

Synthesis and Application of New Amphiphilic Asphaltene Ionic Liquid Polymers to Demulsify Arabic Heavy Petroleum Crude Oil Emulsions.

Asphaltenes are heavy petroleum crude oil components which limit the production of petroleum crude oil due to their aggregation and their stabilization for all petroleum crude oil water emulsions. The present study aimed to modify the chemical structures of isolated asphaltenes by converting them into amphiphilic polymers containing ionic liquid moieties (PILs) to demulsify the emulsion and replace the asphaltene layers surrounding the oil or water droplets in petroleum crude oil emulsions. The literature survey indicated that no modification occurred to produce the PILs from the asphaltenes. In this respect, the asphaltenes were modified via oxidation of the lower aliphatic chain through carboxylation followed by conversion to asphaltene acid chloride that reacted with ethoxylated N-alkyl pyridinium derivatives. Moreover, the carboxylation of asphaltenes was carried out through the Diels-Alder reaction with maleic anhydride that was linked with ethoxylated N-alkyl pyridinium derivatives to produce amphiphilic asphaltene PILs. The produced PILs from asphaltenes acid chloride and maleic anhydride were designated as AIL and AIL-2. The chemical structure and thermal stability of the polymeric asphaltene ionic liquids were evaluated. The modified structure of asphaltenes AIL and AIL-2 exhibited different thermal characteristics involving glass transition temperatures (Tg) at -68 °C and -45 °C, respectively. The new asphaltenes ionic liquids were adsorbed at the asphaltenes surfaces to demulsify the heavy petroleum crude emulsions. The demulsification data indicated that the mixing of AIL and AIL-2 100 at different ratios with ethoxylated N-alkyl pyridinium were demulsified with 100% of the water from different compositions of O:W emulsions 50:50, 90:10, and 10:90. The demulsification times for the 50:50, 90:10, and 10:90 O:W emulsions were 120, 120, and 60 min, respectively. The interaction of the PILs with asphaltene and mechanism of demulsification was also investigated.

E-cadherin and periostin in early detection and progression of diabetic nephropathy: epithelial-to-mesenchymal transition.

BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Many mechanisms are involved in its development; one of these mechanisms is epithelial-to-mesenchymal transition (EMT). During EMT, losing of the epithelial biomarkers like E-cadherin and increasing of mesenchymal biomarkers like periostin are very characteristic. METHODS: The study included 19 healthy controls and 71 DN patients categorized according to their urinary albumin-to-creatinine ratio (UACR) into 19 normoalbuminuric (UACR < 30 mg/g), 37 microalbuminuric (UACR 30-300 mg/g), and 15 macroalbuminuric (UACR > 300 mg/g) patients. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1C%), serum creatinine (Cr), and urea were measured. E-cadherin and periostin were measured by ELISA and compared among groups. RESULTS: Concerning E-cadherin levels, in comparison to control group, there were significantly decreased in all groups (0.94, 0.52, and 0.14 ng/mL in normoalbuminuria, microalbuminuria, and macroalbuminuria groups; respectively). For periostin levels, nonsignificant increase in normoalbuminuria (0.32 ng/mL) than control group (0.3 ng/mL) was observed. There was a significant increase in other groups with the highest values in macroalbuminuria group (1.66 ng/mL). E-cadherin and periostin were correlated with each other (r = - 0.353, P < 0.001). UACR was negatively correlated with E-cadherin and positively correlated with periostin. ROC curve analyses showed that the AUC to diagnose established microalbuminuria using E-cadherin was 0.998 (95% CI 0. 932-1), and using periostin was 0.833 (95% CI 0.709-0.919). CONCLUSION: Serum E-cadherin and periostin could be considered as reliable biomarkers involved in DN pathogenesis and linked to its stages.

Review of Diabetic Polyneuropathy: Pathogenesis, Diagnosis and Management According to the Consensus of Egyptian Experts.

Diabetic polyneuropathy (DPN) is a complex and multifactorial entity in which various factors besides hyperglycemia play an important role. Symptoms of DPN are sensory, motor or autonomic. Intensive research proved that oxidative stress is the common denominator for the four major destructive pathways of hyperglycemia including increased hexosamine pathway flux, activation of Protein kinase-C (PKC) pathway, increased Advanced Glycated End-products (AGEs) formation, and increased Polyol Pathway flux. National data in Egypt confirms that more than 60% of Egyptian diabetic patients suffer from neuropathy. The most common complications of DPN are Cardiac Autonomic Neuropathy (CAN), diabetic foot and ulcers, neuromuscular disability, and anxiety. In addition, DPN affects the Quality of Life (QoL). According to common clinical practice, the common diagnostic tools are bed-side diagnosis and electrophysiological tests. Early diagnosis is critical to improve the prognosis of DPN and therapeutic intervention in the early phase. In this review, we provide a clear understanding of the pathogenesis, early diagnosis and the good management of DPN. Since the pathogenesis of DPN is multifactorial, its management is based on combination therapy of symptomatic; either pharmacological or non-pharmacological treatments, and pathogenic treatment. Alpha Lipoic Acid (ALA) is a potent anti-oxidant that has several advantages as a pathogenic treatment of DPN. So, in clinical practice, ALA may be prescribed for patients with early neuropathic deficits and symptoms. Patient education has an important role in the managemement of DPN.

Epidermal growth factor receptor and podocin predict nephropathy progression in type 2 diabetic patients through interaction with the autophagy influencer ULK-1.

AIMS: Diabetic nephropathy (DN) that progress to end stage renal failure is a serious health problem. Autophagy is involved in DN pathogenesis. Finding renal prognostic biomarkers can help in the future renal status prevision. Therefore, the aim of current study was to evaluate and correlate circulating levels of autophagy regulator protein Unc-51-like kinase 1 (ULK-1) with the widely expressed receptor in mammalian kidney; epidermal growth factor receptor (EGFR); and the key functional podocyte protein podocin (PDCN). METHODS: Serum levels were assessed by ELISA in 72 type 2 diabetic patients classified according to their urinary albumin/creatinine ratio; 19 normoalbuminuric, 37 microalbuminuric and 16 macroalbuminuric patients; age and sex matched with 18 healthy controls. RESULTS: Microalbuminuria and macroalbuminuria patients exhibited decreased ULK-1, EGFR and PDCN levels. Only EGFR showed lower levels in normoalbuminuria compared with controls. ULK-1 and EGFR were significantly higher in normoalbuminuria compared with microalbuminuria and macroalbuminuria patients. ULK-1, EGFR and PDCN were correlated with each other and with some metabolic parameters. CONCLUSIONS: ULK-1 with EGFR can predict early impairment in DN while PDCN can highlight progressive DN risk EGFR and PDCN may interact synergistically with ULK-1 in autophagy dysregulation as a pathogenic mechanism of DN induction and progression.

Role of CTRP3, CTRP9 and MCP-1 for the evaluation of T2DM associated coronary artery disease in Egyptian postmenopausal females.

C1q complement/tumor necrosis factor (TNF)-related protein (CTRP) family comprises of 15 proteins that posses important implications in energy homeostasis, infection and inflammation. However, their roles in diabetes mellitus (DM) and its vascular complications have not been completely assessed. This works aims to study the association of two CTRPs; 3 and 9, with pro-inflammatory cytokine monocyte chemoattractant protein-1 (MCP-1), and biochemical parameters of type 2 diabetes (T2D), dyslipidemia and coronary artery disease (CAD). METHODS: Biochemical markers and serum levels of CTRPs and MCP-1 were measured in 86 postmenopausal females. Subjects were divided over four groups; 13 apparent healthy subjects as control (group I), 29 patients with CAD (group II), 29 patients with T2D ≥5 years (group III) and 15 patients with CAD secondary to T2D (group IV). Serum CTRP3, CTRP9, MCP-1 and insulin were measured by ELISA. RESULTS: Serum CTRP3 levels were found to be significantly higher in group III and IV, whereas, it was significantly lower in group II on comparing to group I. While, CTRP9 levels were significantly decreased in group II, III and IV on comparing to group I. MCP-1 levels were found to be significantly increased in groups II, III and IV on comparison with group I. Both CTRPs were significantly negatively correlated with each other. While MCP-1 was significantly correlated negatively to CTRP9. CONCLUSION: This study associates the possible role of CTRP3, CTRP9 and MCP-1/CCL2 in the diagnosis/prognosis of CAD complication in T2D postmenopausal females.

Serum Vitamin D and Its Upregulated Protein, Thioredoxin Interacting Protein, Are Associated With Beta-Cell Dysfunction in Adult Patients With Type 1 and Type 2 Diabetes.

OBJECTIVES: Diabetes mellitus is characterized by either complete deficiency of insulin secretion, as in type 1 diabetes, or decompensation of the pancreatic beta cells in type 2 diabetes. Both vitamin D (vitD) and thioredoxin interacting protein (TXNIP) have been shown to be involved in beta-cell dysfunction. Therefore, this study was designed to examine vitD and TXNIP serum levels in patients with diabetes and to correlate these levels with beta-cell function markers in both types of diabetes. METHODS: The routine biochemical parameters and the serum levels of vitD and TXNIP were measured in 20 patients with type 1 diabetes and 20 patients with type 2 diabetes. The levels were then compared to those of 15 healthy control volunteers. Insulin, C-peptide and proinsulin (PI), vitD and TXNIP were measured by ELISA. Beta-cell dysfunction was assessed by homeostatic model assessment (HOMA-beta), proinsulin-to-C-peptide (PI/C) and proinsulin-to-insulin (PI/I) ratios. Correlations among various parameters were studied. RESULTS: Patients with type 1 diabetes had significantly lower HOMA-beta, vitD and TXNIP levels; however, they had higher PI/C levels than the control group. Meanwhile, patients with type 2 diabetes had significantly higher C-peptide, proinsulin, PI/C, HOMA-insulin resistance (HOMA-IR) and lower HOMA-beta and vitD levels, with no significant difference in TXNIP levels as compared to the control group. In addition, vitD was significantly correlated positively with HOMA-beta and TXNIP and negatively with PI, PI/C, PI/I and HOMA-IR. TXNIP correlated positively with HOMA-beta and negatively with PI/C. CONCLUSIONS: Our data showed that vitD and TXNIP were associated with different beta-cell dysfunction markers, indicating their potential abilities to predict the beta-cell status in people with diabetes.