The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to individuals with underlying chronic kidney disease (CKD). People with CKD are immunocompromised and therefore result in poorer outcomes including increased risk of hospitalization and mortality after COVID-19.1 Despite the availability of COVID-19 vaccines, current data on the vaccine efficacy in individuals with CKD are limited to surrogate endpoints such as antibody titers. As a result, a dedicated study is required to evaluate the effectiveness and safety of COVID-19 vaccines for the CKD population

Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Additive renoprotective effects of B2-kinin receptor blocker and PPAR-γ agonist in uninephrectomized db/db mice

We recently showed that the bradykinin B2 receptor (B2R) blocker icatibant (Icat) and the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (Ros) exerted anti-inflammatory effects in renal tubular cells exposed to a diabetic milieu. This study aims to explore whether these effects can be translated to an experimental model of type 2 diabetic nephropathy (DN). db/db mice and their nondiabetic db/m littermates underwent sham operation or uninephrectomy (Unx) at 10 weeks and received vehicle (Veh), metformin (Met), Icat, Ros, or Icat plus Ros for 8 weeks before killing. Among the db/db group with Unx, mice that received Icat or Ros had significantly lower serum creatinine and albuminuria, which was further reduced when Icat and Ros were given in combination. These beneficial effects were not observed in the Met group that achieved similar glycemic control as Ros-treated animals. Likewise, the severity of reactive glomerular and proximal tubular hypertrophy, glomerulosclerosis, interstitial injury, cortical F4/80 and α-smooth muscle actin immunostaining, and CCL-2, ICAM-1 and TGF-Β overexpression were all attenuated by Icat and Ros, and these effects were enhanced when both agents were combined. Immunohistochemical staining confirmed the proximal tubular expression of CCL-2 (inflammation) and TGF-Β (fibrosis). Treatment with Icat was associated with decreased B2R, but increased, B1R expression, which was exaggerated in Unx animals. At the signaling level, Icat and Ros reduced extracellular signal-regulated kinase 1/2 and STAT1 activation, respectively. Our results suggest a deleterious role of the kallikrein-kinin system in murine-accelerated DN, which can be ameliorated by the B2R blocker Icat and enhanced by the addition of Ros. This calls for further evaluation of this novel therapeutic approach in more animal models of diabetic nephropathy. © 2011 USCAP, Inc All rights reserved.link_to_subscribed_fulltex

Renoprotection by Rosiglitazone in Accelerated Type 2 Diabetic Nephropathy: Role of STAT1 Inhibition and Nephrin Restoration

Background: Rosiglitazone (Ros) has been shown to attenuate CXCL8 and ICAM-1 overexpression in renal tubular cells exposed to glycated albumin. The present study explores whether this can be translated into renoprotection in vivo. Uninephrectomized (Unx) type 2 diabetic db/db mice were chosen as a model of accelerated diabetic nephropathy. Methods: Uninephrectomy was performed in 10-week-old db/db mice. They were then treated with vehicle, metformin or Ros for 8 weeks. Results: Unx-db/db mice treated with Ros had lower serum creatinine and albuminuria, less severe glomerulosclerosis, tubulointerstitial injury, fewer infiltrating macrophages, and less proliferating nuclear antigen-positive tubular cells compared with mice treated with metformin that had a similar level of glycemic control and insulin resistance. In addition, Ros but not metformin attenuated renal cortical expression of CCL2, MIP-2, and ICAM-1 and inhibited p-STAT1 signal activation. Ros also increased glomerular nephrin expression. Conclusions: Our results delineated the biochemical and histologic characteristics of Unx-db/db mice and demonstrated the in vivo glucose-independent anti-inflammatory mechanisms of Ros in nephropathy of accelerated murine type 2 diabetes. Copyright © 2010 S. Karger AG, Basel.link_to_subscribed_fulltex

The compatibility of individual herbs in Erxian Decoction, an anti-menopausal herbal formula, for treating osteoporosis

BACKGROUND: Premenopausal osteoporosis is one of the syndromes in postmenopausal women, which is associated with the estrogen deficient state (1, 2). Estrogen deficiency would lead to increased receptor activator of nuclear factor kappa-B ligand (RANKL) which binds to RANKL receptor of osteoclast precursor triggering osteoclastogenesis (3-5). Estrogen deficieny will also suppress the expression of osteoprotegerin (OPG), which can bind and inhibit the action of RANKL (6). Risk of bone fracture increase when the balance between bone formation and bone resorption is tipped (7). Erxian Decoction (EXD) has been used for relieving menopausal symptoms for more than fifty years. It is composed of six herbs namely Rhizome curculiginis, Herba epimedii, Radix Morindae officinalis, Rhizome anemarrhenae, Cortex phellodendri, and Radix Angelicae sinenisis. It is reported that EXD can stimulate ovarian estrogen production (8) and also possesses anti-osteoporotic properties (9). However, the compatibility and the role of different herbs in EXD formula in treating osteoporosis have not been reported. The effects of EXD and its component herbs on proliferation of human fetal osteoblast cell (hFOB 1.19), murine macrophage-like osteoclast precusor (RAW 264.7), OPG secretion, and the molecular signaling involved in osteoclastogenesis have been investigated in this study. RESULTS AND DISCUSSION: Our results showed that EXD could significantly stimulate proliferation of hFOB 1.19 while inhibit proliferation of RAW264.7. The inhibitory effect on RAW 264.7 was most prominent in cells treated with Herba epimedii alone, and this inhibitory effect was not observed in cell treated with EXD without Herba epimedii. This indicates that the anti-osteoporotic efficacy is contributed largely by Herba epimedii in term of regulating the proliferation of osteoclast precursor. The stimulatory effect of hFOB 1.19 was most prominent in cell treated with Radix Morindae officinalis, and such stimulatory effect was also eliminated in EXD without Radix Morindae officinalis. Thus the stimulation of osteoblast proliferation by EXD was due to the presence of Radix Morindae officinalis. The measure of osteoblast secreted OPG has also revealed that EXD can significantly increase OPG production from hFOB 1.19 cells. The increased in OPG was only observed in EXD, suggesting that different individual herbs exerted mutual effect in stimulating OPG production by EXD, thus inhibiting the osteoclastogenic effect of RANKL. In the differentiation assay, in which EXD could significantly suppress the differentiation of RAW 264.7 cells into osteoclasts, as signified by the lower number of multi-nucleated cells detected by mature osteoclast marker tartrate-resistant acid phosphatase (TRAP) staining method. The inhibitory effect of osteoclast differentiation was mainly mediated by Herba epimedii, as the inhibitory effect was less prominent in treatment of EXD without Herba epimedii. CONCLUSION: Our results have demonstrated the potent anti-osteoporotic effect of EXD in vitro. The anti-osteoporotic effects of EXD could due to the anti-proliferation of osteoclast precursor cells and stimulatory effect of osteoblast cells. These effects are contributed by different herbs in the EXD formula, in which the effect on osteoclast was mainly contributed by Herba epimedii and the effect on osteoblast was mainly due to Radix Morindae officinalis. The six component herbs could also exert stimulatory effect on osteoblast OPG production in the EXD formula but not in single herbs alone. EXD could also inhibit differentiation of RAW 264.7 into mature osteoclast which was also mainly mediated by Herba epimedii. Our results have demonstrated the anti-osteoporotic effect of EXD and its component herbs, and suggested the possible interaction and compatibility of component herbs in an anti-menopausal Chinese medicine formulation.The 13th World Congress on Menopause (IMS Roma 2011), Rome, Italy, 8-11 June 2011

Differential effects of advanced glycation end-products on renal tubular cell inflammation

Aim: The authors recently showed that advanced glycation end-products (AGE) in the form of glycated albumin (GA) upregulated renal tubular expression of interleukin (IL)-8 and soluble intercellular adhesion molecule-1 (sICAM-1), but not other important cytokines known to mediate diabetic nephropathy. This implies that other molecules such as the carbonyl intermediates of AGE or other modified protein lysine-albumin may participate in diabetic tubular injury. Methods: Human proximal tubular epithelial cells (PTEC) were growth-arrested and exposed to methylglyoxal (MG), MG-bovine serum albumin (BSA)-AGE, carboxymethyllysine (CML)-BSA, AGE-BSA or BSA with or without prior addition of rosiglitazone that was previously shown to attenuate the pro-inflammatory effect of GA alone. Results: MG-BSA-AGE and AGE-BSA upregulated tubular expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF), whereas CML-BSA stimulated expression of IL-6, CCL-2, CTGF, TGF-β and VEGF. These AGE compounds also activated nuclear factor (NF)-ÎB and their effects were attenuated by pre-incubation with anti-RAGE antibody. MG and BSA did not affect the expression of any of these molecules. Rosiglitazone did not affect the in vitro biological effects of MG, MG-BSA-AGE, AGE-BSA or CML-BSA on PTEC. Conclusion: AGE exhibit differential inflammatory and fibrotic effects on PTEC via RAGE activation and NF-ÎB signal transduction. Rosiglitazone had no effect on these responses. Further investigations on compounds that nullify the downstream effects of these AGE are warranted. Tang and colleagues showed that various AGE formation (MG-BSA-AGE, AGE-BSA and CML-BSA are important AGE) have differential pro-inflammatory and profibrotic effects on cultured PTEC via RAGE activation and NF-ÎB signal transduction. © 2011 Asian Pacific Society of Nephrology.link_to_subscribed_fulltex