Time-restricted feeding's effect on overweight and obese patients with chronic kidney disease stages 3-4: A prospective non-randomized control pilot study.

Background: Time-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy. Methods: This is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks. Results: The change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 µmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction. Conclusion: Preliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.

Self-management program for patients with chronic kidney disease (SMP-CKD) in Southern China: protocol for an ambispective cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. METHODS: In this ambispective intervention cohort study,1,200 patients with CKD stages 1-5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1-2 and trimonthly in stage 3-5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. DISCUSSION: This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378.

Increasing CCL5/CCR5 on CD4+ T cells in peripheral blood of oral lichen planus.

Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa, in which T helper 1 (Th1) cells are greatly involved. Chemokine CCL5 is required for T cells infiltration and activation. CCR5, one of its receptors, specifically expressed on Th1 cells among CD4(+) T cells, can be up-regulated by Th1 cytokines like interleukin2 (IL-2) and interferon-gamma (IFN-γ), and down-regulated by Th2 cytokines like IL-4. The present study aimed to determine whether CCL5 and CCR5 had effects on the immune response of OLP. We analyzed the proportion of CCR5(+)CD4(+) T cells in CD4(+) T cells using flow cytometry and the serum levels of CCL5, IL-2, IFN-γ, and IL-4 with ELISA. MicroRNA-125a (miR-125a), a blocker of CCL5, was examined with RT-PCR. The results showed both the serum CCL5 and the percentage of CCR5(+)CD4(+) T cells elevated in OLP patients. Serum IL-2 and IFN-γ increased in OLP patients, but IL-4 decreased. MiR-125a was down-regulated in OLP patients, and there was a negative correlation between miR-125a content and the OLP severity which was measured with a RAE (reticular, atrophic and erosive lesion) scoring system. In conclusion, increasing CCl5/CCR5 might participate in the immune response of OLP. Th1-type cytokines environment presented in OLP probably performed as a magnifier for the CCR5. Moreover, miR-125a might be a candidate biomarker to estimate the severity of OLP.

Increased B7-H1 expression on peripheral blood T cells in oral lichen planus correlated with disease severity.

BACKGROUND: Oral lichen planus (OLP) is a chronic and T cell-mediated autoimmune disease whose immunopathogenesis may involve antigen-presentation, T cells activation and migration as well as keratinocytes apoptosis. PD-1/B7-H1 pathway may have a unique function in regulating self-reactive T cells associated with inflammatory response and maintaining tolerance in peripheral tissues. In this study, we aimed to explore the contribution of PD-1/B7-H1 pathway to OLP. METHODS: We determined the expression of PD-1 and B7-H1 on peripheral blood T cells from OLP cases and analyzed their association with disease severity assessed by RAE (reticular, atrophic and erosive lesion) scoring system. In addition, interferon-γ, interleukin (IL)-2, IL-4, IL-10 and soluble PD-1 concentrations in serum were measured using ELISA. Then, we explored the regulation of PD-1/B7-H1 pathway on T cells immune response in OLP by blockade of PD-1 or B7-H1. RESULTS: We found that PD-1 and B7-H1 were up-regulated on peripheral blood T cells from OLP patients and B7-H1 expression positively correlated with disease severity of OLP. It is suggested that Th1 dominant inflammatory situation might contribute to the high expression of PD-1 and B7-H1 in OLP. Blockade of PD-1/B7-H1 pathway significantly increased the proliferation, and IFN-γ and IL-2 production of T cells. CONCLUSIONS: PD-1/B7-H1 pathway may play an important role in negatively modulating T cell-mediated immune response in OLP, and provide the rationale to employ B7-H1 expression on peripheral blood T cells as a marker of severity of OLP and to develop agonists targeting PD-1/B7-H1 pathway as a promising immunotherapeutic strategy for OLP.

Biologics, an alternative therapeutic approach for oral lichen planus.

Oral lichen planus (OLP) is generally accepted as a chronic and T-cell-mediated autoimmune disease, whose immunopathogenesis may involve antigen presentation, T-cell activation and migration as well as, possibly, tumor necrosis factor-alpha (TNF-α)-induced keratinocytes apoptosis. However, present treatment options for OLP are far from being satisfactory. Recent advances in understanding the pathogenesis of OLP, progress in biologics, and the success of biologic therapies in OLP indicate that biologic agents are facing expanding indications in OLP. In this review, we mainly discuss the role of T cells in the pathogenesis of OLP and several biologic therapies that directly and/or indirectly target T cells to treat OLP.

Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form.

BACKGROUND: Nuclear factor-kappa B (NF-kappaB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) in OLP and their expression pattern in relation to several clinical features. METHODS: Thirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-kappaB p65 and TNF-alpha of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls. RESULTS: Nuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-alpha staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-kappaB p65 and TNF-alpha were significantly different with respect to clinical forms and lesion sites (P < 0.05), except for genders (P > 0.05) in 30 OLP cases. NF-kappaB nuclear staining positively correlated (r = 0.676, P < 0.01) with TNF-alpha overexpression in OLP. CONCLUSIONS: Nuclear factor-kappa B activation and its correlation with overexpression of TNF-alpha may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-kappaB and TNF-alpha, which may contribute to inflammation in OLP; NF-kappaB may also protect epithelial keratinocytes from excessive apoptosis.