Upregulation of MTOR,RPS6KB1, and EIF4EBP1 in the whole blood samples of Iranian patients with multiple sclerosis compared to healthy controls

Metabolic Brain Disease - Various genetic and epigenetic mechanisms have been suggested to play roles as the underlying pathophysiology of Multiple Sclerosis (MS). Changes in different parts of the...     

1, 25-Dihydroxyvitamin D3 activates Apelin/APJ system and inhibits the production of adhesion molecules and inflammatory mediators in LPS-activated RAW264.7 cells

Background1, 25-Dihydroxyvitamin D3 (1, 25(OH)₂D₃), an active form of vitamin D3, plays a crucial role in the mitigation of inflammation damage. Recent studies have revealed that apelin and its receptor (apelin/APJ system) could significantly ameliorate LPS-induced inflammation-response. This investigation aimed to appraise the effects of 1, 25(OH)₂D₃ on the apelin/APJ system and production of adhesion molecules and inflammatory mediators in LPS–activated RAW264.7 macrophage cells.MethodsMurine RAW264.7 cells were pretreated with 1, 25(OH)₂D₃, followed stimulation with LPS (1 μg/mL) for 24 h. The effect of 1, 25(OH)₂D₃ on LPS-induced cell injury was determined by MTT assay, whereas, enzyme-linked immunosorbent assay (ELISA), qPCR and western blotting were used to evaluate cytokine production and apelin/APJ system expression. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) protein expression were measured by flow cytometry.ResultsThe levels of IL-1β, IL-6, and TNF-α cytokines were significantly increased by incubation with LPS. LPS also increased the protein expression of adhesion molecules, including VCAM-1 and ICAM-1. However, pretreatment with 1, 25(OH)₂D₃ markedly inhibited LPS-induced production of inflammatory cytokines and adhesion molecules. Moreover, we found that 1, 25(OH)₂D₃ could induced the apelin/APJ system expression. Further experiments demonstrated the significant increase of apelin/APJ system expression at both the protein and mRNA levels in LPS-activated cells when pretreated with 1, 25(OH)₂D₃.ConclusionTaken together, our results indicated that 1, 25(OH)₂D₃ confers an anti-inflammatory effect through a likely mechanism involving a reduction in pro-inflammatory mediators and adhesion molecules via up-regulation of the apelin/APJ system in RAW264.7 cells.     

Synthesis of bioactive polyaniline-b-polyacrylic acid copolymer nanofibrils as an effective antibacterial and anticancer agent in cancer therapy,especially for HT29 treatment

In this work, a new highly water-soluble copolymer of polyacrylic acid with polyaniline is introduced. Acrylic acid was polymerized via the Reversible Addition Fragmentation Chain Transfer method (RAFT) in the presence of an initiator and the obtained polyacrylic acid was copolymerized with aniline at room temperature. As the main achievements of this work, the resulting block copolymer with nanosized structure revealed favorable solubility in polar solvents, as well as excellent antibacterial and anticancer activities. Therefore, it is an appropriate candidate for medical applications such as wound healing and cancer therapy, especially in HT29 treatment.

In this work, a new highly water-soluble copolymer of polyacrylic acid with polyaniline is introduced.     

Transmembrane serine protease 2 and angiotensin-converting enzyme 2 anti-inflammatory receptors for COVID-19/inflammatory bowel diseases treatment

Inflammatory bowel diseases (IBD) refer to a subgroup of chronic, progressive, long-term, and relapsing inflammatory disorders. IBD may spontaneously grow in the colon, and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine. Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019 (COVID-19). Currently, the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide. It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment. Generally, viral entry causes a 'cytokine storm' that induces excessive generation of proinflammatory cytokines/chemokines including interleukin (IL)-6, IL-2, IL-7, tumor necrosis factor-α, and interferon-γ. Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19. Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular. Data from clinical, in vitro, and in vivo studies were collected in English from PubMed, Google Scholar, Scopus, and the Cochrane library until May 2021.     

Bioactive polymeric scaffolds for osteogenic repair and bone regenerative medicine

The loss of bone tissue is a striking challenge in orthopedic surgery. Tissue engineering using various advanced biofunctional materials is considered a promising approach for the regeneration and substitution of impaired bone tissues. Recently, polymeric supportive scaffolds and biomaterials have been used to rationally promote the generation of new bone tissues. To restore the bone tissue in this context, biofunctional polymeric materials with significant mechanical robustness together with embedded materials can act as a supportive matrix for cellular proliferation, adhesion, and osteogenic differentiation. The osteogenic regeneration to replace defective tissues demands greater calcium deposits, high alkaline phosphatase activity, and profound upregulation of osteocalcin as a late osteogenic marker. Ideally, the bioactive polymeric scaffolds (BPSs) utilized for bone tissue engineering should impose no detrimental impacts and function as a carrier for the controlled delivery and release of the loaded molecules necessary for the bone tissue regeneration. In this review, we provide comprehensive insights into different synthetic and natural polymers used for the regeneration of bone tissue and discuss various technologies applied for the engineering of BPSs and their physicomechanical properties and biological effects.     

HBsAg level at time of liver transplantation determines HBsAg decrease and anti-HBs increase and affects HBV DNA decrease during early immunoglobulin administration

BACKGROUND/AIMS: Administration of hepatitis B immunoglobulin (HBIG) initially after liver transplantation of hepatitis B patients is considered important to prevent reinfection reliably. However, dosing schedules differ considerably between centers. We measured HBsAg, anti-HBs and HBV DNA kinetics to create a rational basis for dosing schemes. METHODS: Thirteen patients (group A) received 10,000 IU HBIG in the anhepatic phase followed by 10,000 IU daily until HBsAg became negative, whereas five patients (group B) received 20,000 IU followed by 5000 IU every 30 min. RESULTS: HBsAg levels at time of transplantation ranged from 0.12 to 12,990 IU/ml. Correlations between initial HBsAg and HBIG required to decrease HBsAg below 1 IU/ml were high in groups A and B (r=0.97, p<0.001; r=1.00, p<0.001), as were correlations between initial HBsAg and HBIG required to raise anti-HBs above 1000 IU/l (r=0.94, p<0.001; r=1.00, p<0.001). In 11 HBV DNA-positive patients, DNA levels became negative in seven, and dropped by 2.5 log10 (mean) in the other four patients during immunoglobulin administration. CONCLUSIONS: In conclusion, required HBIG doses to decrease HBsAg and raise anti-HBs are determined by HBsAg levels at time of transplantation, not by HBV DNA levels. Shortened HBIG dosing intervals accelerate HBsAg decrease and anti-HBs increase. HBV DNA decreases rapidly during HBIG administration in most patients.     

Glycemic Control and Survival in Peritoneal Dialysis Patients with Diabetes Mellitus

Summary

Background and objectives

The optimal target for glycemic control has not been established for diabetic peritoneal dialysis (PD) patients.

Design, setting, participants, & measurements

We examined mortality-predictability of hemoglobin A1c random serum glucose in a contemporary cohort of diabetic PD patients treated in DaVita dialysis clinics July 2001 through June 2006 with follow-up through June 2007.

Results

We identified 2798 diabetic PD patients with A1c data. Serum glucose correlated with A1C (r = 0.51). Adjusted all-cause death hazard ratio and 95% confidence interval for baseline A1c increments of 7.0 to 7.9%, 8.0 to 8.9%, 9.0 to 9.9%, and ≥10%, compared with 6.0 to 6.9% (reference), were 1.13 (0.97 to 1.32), 1.05 (0.88 to 1.27), 1.06 (0.84 to 1.34), and 1.48 (1.18 to 1.86); and for time-averaged A1c values were 1.10 (0.96 to 1.27), 1.28 (1.07 to 1.53), 1.34 (1.05 to 1.70), and 1.81 (1.33 to 2.46), respectively. The A1c-mortality association was modified by hemoglobin level such that higher all-cause mortality was evident only in nonanemic patients. Similar but non-significant trends in cardiovascular death risk was found across A1c increments. Adjusted all-cause death HR for time-averaged blood glucose 150 to 199, 200 to 249, 250 to 299, and ≥300 mg/dl, compared with 60 to 99 mg/dl (reference), were 1.02 (0.70 to 1.47), 1.12 (0.77 to 1.63), 1.45 (0.97 to 2.18), and 2.10 (1.37 to 3.20), respectively.

Conclusions

Poor glycemic control appears associated incrementally with higher mortality in PD patients. Moderate to severe hyperglycemia is associated with higher death risk especially in certain subgroups.