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Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreases, blood, guts, and nervous systems of mice, but their effect on kidney disease is unknown. In addition, a FMD has not been tested in rats. Here, we show that cycles of a newly developed low-salt FMD (LS-FMD) restored normal proteinuria and nephron structure and function in rats with puromycin-induced nephrosis compared with that in animals with renal damage that did not receive the dietary intervention. LS-FMD induced modulation of a nephrogenic gene program, resembling renal developmental processes in multiple kidney structures. LS-FMD also activated podocyte-lineage reprogramming pathways and promoted a quiescent state in mature podocytes in the rat kidney damage model. In a pilot clinical study in patients with chronic kidney disease, FMD cycles of 5 days each month for 3 months promoted renoprotection, including reduction of proteinuria and improved endothelial function, compared with that in patients who did not receive the FMD cycles. These results show that FMD cycles, which promote the reprogramming of multiple renal cell types and lead to glomerular damage reversal in rats, should be tested further for the treatment of progressive kidney diseases.

Objective: We studied the role of caffeine intake on endothelial function in SLE by assessing its effect on circulating endothelial progenitor cells (EPCs) both ex vivo in SLE patients and in vitro in healthy donors (HD) treated with SLE sera., Methods: We enrolled SLE patients without traditional cardiovascular risks factors. Caffeine intake was evaluated with a 7-day food frequency questionnaire. EPCs percentage was assessed by flow cytometry analysis and, subsequently, EPCs pooled from six HD were co-cultured with caffeine with and without SLE sera. After 7 days, we evaluated cells' morphology and ability to form colonies, the percentage of apoptotic cells by flow cytometry analysis and the levels of autophagy and apoptotic markers by western blot. Finally, we performed a western blot analysis to assess the A2AR/SIRT3/AMPK pathway., Results: We enrolled 31 SLE patients, and observed a positive correlation between caffeine intake and circulating EPCs percentage. HD EPCs treated with SLE sera and caffeine showed an improvement in morphology and in number of EPCs colony-forming units in comparison with those incubated without caffeine. Caffeine was able to restore autophagy and apoptotic markers in HD EPCs as before SLE sera treatment. Finally, caffeine treatment was able to significantly reduce A2AR levels, leading to an increase in protein levels of SIRT3 and subsequently AMPK phosphorylation., Conclusions: Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To provide an updated systematic review and meta-analysis with meta-regression of efficacy and safety of fenestrated/branched endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) compared with open repair., Background: Endovascular repair of TAAAs may be a promising alternative to open surgery by reducing invasiveness and expanding the eligible population, but evidence remains limited., Methods: We applied "Prepared Items for Systematic Reviews and Meta-analysis" guidelines to retrieve, quantitatively pool, and critically evaluate the efficacy and safety (including 30-day mortality, reintervention, spinal cord injury [SCI], and renal injury) of both approaches. Original studies were retrieved from PubMed, Embase, and Cochrane Library until April 20, 2022, excluding papers reporting <10 patients. Pooled proportions and means were determined using a random-effect model. Heterogeneity between studies was evaluated with I2 statistics., Results: Sixty-four studies met the predefined inclusion criteria. Endovascular cohort patients were older and had higher rates of comorbidities. Endovascular repair was associated with similar proportions of mortality (0.07, 95% confidence intervals [CI]: 0.06-0.08) compared with open repair (0.09, 95% CI: 0.08-0.12; P = 0.22), higher proportions of reintervention (0.19, 95% CI: 0.13-0.26 vs 0.06, 95% CI: 0.04-0.10; P < 0.01), similar proportions of transient SCI (0.07, 95% CI: 0.05-0.09 vs 0.06, 95% CI: 0.05-0.08; P = 0.28), lower proportions of permanent SCI (0.04, 95% CI: 0.03-0.05 vs 0.06, 95% CI: 0.05-0.07; P < 0.01), and renal injury (0.08, 95% CI: 0.06-0.10 vs 0.13, 95% CI: 0.09-0.17; P = 0.02). Results were affected by high heterogeneity and potential publication bias., Conclusions: Despite these limitations and the lack of randomized trials, this meta-analysis suggests that endovascular TAAA repair could be a safer alternative to the open approach., Competing Interests: L.B. has received consulting fees and grants from Cook Medical, W. L. Gore, Artivion. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-COVID-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up-modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans, as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of the mannose receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of COVID-19 pathology and immunity to SARS-CoV-2.