Chronic Disease Processes Research Articles

Senolytic procyanidin C1 alleviates renal fibrosis by promoting apoptosis of senescent renal tubular epithelial cells.

Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) in renal tissues plays an important role in the development of renal fibrosis. Eliminating senescent TECs has been proven to effectively reduce renal fibrosis. Procyanidin C1 (PCC1) plays a senolytic role by specifically eliminating senescent cells and extending its overall lifespan. However, whether PCC1 can alleviate unilateral ureteral obstruction (UUO)-induced renal fibrosis and the associated therapeutic mechanisms remains unclear. Here, we observed a marked increase in senescent TECs within obstructed human renal tissue and demonstrated the positive correlation between the accumulation of senescent TECs and renal fibrosis in UUO-induced renal fibrosis in mice. We found that PCC1 reduced the number of senescent TECs, restored the regenerative phenotype in kidneys with reduced fibrosis, and improved tubular repair after UUO-induced injury. Invitro, PCC1 effectively cleared senescent HK2 cells by inducing apoptosis via ANGPTL4/NOX4 signaling. Incubation with culture medium from senescent HK2 cells promoted fibroblast activation, whereas PCC1 impeded profibrotic effects by downregulating senescence-associated secretory phenotype (SASP) factors from senescent HK2 cells. Therefore, PCC1 alleviated interstitial renal fibrosis not only by clearing senescent TECs and improving tubular repair but also by indirectly attenuating myofibroblast activation by reducing the level of SASP. In summary, PCC1 may be a novel therapeutic senolytic agent for treating renal fibrosis.

Alterations in Autophagic Function and Endoplasmic Reticulum Stress Markers in the Peripheral Blood Mononuclear Cells of Patients on Hemodialysis.

Oxidative stress, endoplasmic reticulum (ER) stress, and alterations in autophagy activity have been described as prominent factors mediating many pathological processes in chronic kidney disease (CKD). The accumulation of misfolded proteins in the ER may stimulate the unfolded protein response (UPR). The interplay between autophagy and UPR in hemodialysis (HD) patients remains unclear. The aim of the present study was to explore the associations between serum oxidative stress markers, autophagy activity, and ER stress markers in the peripheral blood mononuclear cells (PBMCs) of patients on HD. Autophagy and ER stress-related protein expression levels in PBMCs were measured using western blotting. The redox state of human serum albumin was measured via high-performance liquid chromatography. Levels of the microtubule associated protein light chain 3 (LC3)-II, BECLIN1, and p62/SQSTM1 proteins were significantly increased in PBMCs of HD patients compared to healthy subjects. The PBMCs in HD patients also displayed augmented glucose-regulated protein 78 kDa (GRP78), phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (p-eIF2α), and activating transcription factor 6 (ATF6) levels (p < 0.05). Additionally, nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) levels were elevated in the PBMCs of HD patients, compared to those of healthy subjects. Correlation analysis showed that the redox status of albumin was significantly correlated with the p62 protein level in PBMCs. Compared to healthy controls, we found elevated autophagosome formation in HD patients. Increased expression of ER stress markers was also observed in HD patients. Furthermore, increased p62 expression was positively correlated with the protein expression of NRF2, as well as a reduced form of serum albumin (human mercaptalbumin; HMA), in HD patients.

Pansitopenia as a Marker of Advanced Human Immunodeficiency Virus (HIV) infection: How Often? A Case Study Accompanied by Literature

Pansitopenia is a condition characterized by anemia, thrombocytopenia, and leukopenia. One of the common etiologies of Pansitopenia is HIV infection. In advanced HIV, Pansitopenia may present even without other clinical findings leading to a diagnosis of HIV. This study was conducted as a case study of a 34-year-old man who presented with chief complaints of chronic diarrhea and fever that lasted for one month. Laboratory examination showed Pansitopenia, HIV-rapid reactive and peripheral blood picture indicating Pansitopenia/ aplastic anemia. Data were collected through history taking, physical examination, and a series of laboratory tests. The patient was diagnosed with Pansitopenia suspected to be caused by HIV infection. The chief complaints of chronic diarrhea and fever suggested a chronic disease process due to immune compromise, as seen in the patient's clinical status indicating advanced HIV. The literature suggests that the severity of pansitopenia depends on the severity of HIV disease. Pansitopenia can be an indicator of the advanced stage of HIV infection. Appropriate management and regular monitoring are essential to prevent further complications. Pansitopenia in HIV patients can be considered as an important indicator to assess the severity of the infection. Prompt treatment and antiretroviral therapy are highly recommended to improve the prognosis of patients.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Interlinking pathways: a narrative review on the role of IL-6 in cancer and atherosclerosis.

Interleukin-6 (IL-6) plays multifaceted roles in cancer and atherosclerosis. Initially recognized for its role in immune response and inflammation, IL-6 promotes tumor progression via the JAK-STAT and MAP kinase pathways and is associated with poor cancer prognoses. In atherosclerosis, IL-6 contributes to endothelial dysfunction and plaque formation. This review highlights the shared inflammatory mechanisms of IL-6 in both diseases and explores the regulatory dynamics of IL-6 signaling, including gene polymorphisms and epigenetic modifications. Google Scholar, Scopus, and PubMed were searched for English-language articles on IL-6 and those reporting shared pathogenic mechanisms of IL-6 in cancer and atherosclerosis from their inception through June 2024. The investigation into IL-6's mechanisms in cancer and atherosclerosis reveals the intricate and interconnected nature of inflammatory processes in chronic diseases. The role of IL-6 in both conditions underscores its centrality in disease pathology, particularly through its involvement in inflammation, immune modulation, and cellular proliferation. This commonality highlights IL-6 as a key player linking these seemingly distinct diseases. Given the shared pathogenic mechanism of IL-6 in cancer and atherosclerosis, this narrative review concludes by emphasizing the therapeutic potential of modulating IL-6 in treating both cancer and atherosclerosis. It advocates for personalized treatment strategies that combine targeted therapies with lifestyle modifications. This holistic approach is considered crucial for effective disease management, given the diverse and complex roles IL-6 plays in these widespread conditions.

Sulforaphane alleviates renal fibrosis through dual regulation on mTOR-mediated autophagy pathway.

Renal fibrosis is a common pathological process of progressive chronic kidney disease (CKD). However, effective therapy is constrained currently. Autophagy is an important mechanism in kidney injury and repairment but its exact role in renal fibrosis was discrepant according to previous studies. Sulforaphane (SFN), a natural plant compound, has been explored as a promising nutritional therapy for a variety of diseases. But the salutary effect and underlying mechanism of SFN on CKD have not been fully elucidated. In this study, we investigated the effect of SFN on renal fibrosis in unilateral ureteral obstruction (UUO) mice. Then we examined the regulatory effect of SFN on autophagy-related proteins in renal fibroblasts and renal tubular epithelial cells. Our results showed that sulforaphane could significantly alleviate renal fibrosis in UUO mice. In vitro, the expression levels of autophagy-related protein showed that SFN could upregulate the autophagy activity of renal interstitial fibroblasts and downregulate the autophagy activity of renal tubular epithelial cells. Furthermore, we found that phosphorylated mTOR protein levels was reduced in renal fibroblasts and increased in renal tubular epithelial cells after SFN treatment. Our results strongly suggested that SFN could alleviate renal fibrosis through dual regulation of mTOR-mediated autophagy pathway. This finding may provide a new perspective on the renal salutary effect of SFN and provide a preclinical rationale for exploring the therapeutic potential of SFN to slow down renal fibrosis.

Research Progress on Natural Products Alleviating Liver Inflammation and Fibrosis via NF-κB Pathway.

Liver fibrosis is a key pathological process in chronic liver diseases, regulated by various cytokines and signaling pathways. Among these, the NF-κB signaling pathway plays a significant role in the initiation and progression of liver fibrosis. Recently, natural products have garnered attention as potential anti-fibrotic agents. This review highlights recent studies on how natural products, including flavonoids, terpenoids, polysaccharides, phenols, alkaloids, quinones, phenylpropanoids, steroids, and nitrogen compounds, mitigate liver fibrosis by modulating the NF-κB signaling pathway. Specifically, it examines how these natural products influence NF-κB activation, nuclear translocation, and downstream signaling, thereby inhibiting inflammatory responses, reducing apoptosis, and regulating hepatic stellate cell (HSC) activity, ultimately achieving therapeutic effects against liver fibrosis. A deeper understanding of the mechanisms by which natural products regulate the NF-κB signaling pathway can provide crucial theoretical foundations and valuable insights for the development of novel anti-fibrotic drugs.

Can Fasting Practices Improve Vitamin D Levels?

Vitamin D deficiency is emerging as a very serious public health problem. Numerous epidemiological studies link vitamin D deficiency to the pathophysiological process of several acute and chronic diseases. Sun exposure, vitamin D supplementation, and fortification of foods with vitamin D are the present strategies adopted to tackle this epidemic. While this can be effective, recent evidence suggests the need to consider the multifaceted causation of vitamin D deficiency such as impaired liver function, kidney function, hyperparathyroidism, and endocrine dysfunction. Therapeutic fasting, a popular nutritional approach has shown to have a positive association with vitamin D levels. This perspective attempts to provide an overview of literature discussing fasting and vitamin D, the possible mechanisms behind this association, and discusses the future possibilities of using fasting as a public/clinical tool in mitigating vitamin D deficiency.

Adipose-derived mesenchymal stem cells inhibit hepatic stellate cells activation to alleviate liver fibrosis via Hippo pathway

BackgroundLiver fibrosis is a common pathological process of chronic liver disease, characterized by excessive deposition of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been found to have potential therapy effect on liver fibrosis, but the mechanism involved was still unclear. The objective of this study is to investigate the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADMSCs) on the treatment of liver fibrosis, with particular emphasis on elucidating the underlying mechanism of action through which ADMSCs inhibit the activation of hepatic stellate cells (HSCs).MethodsADMSCs were isolated from adipose tissue and injected intravenously into hepatic fibrosis model of rats. The histopathological changes, liver function, collagen deposition, the expression of fibroin and Hippo pathway were evaluated. In vitro, ADMSCs were co-cultured with HSCs activated by transforming growth factor beta 1 (TGF-β1), and the inhibitor of Hippo pathway was used to evaluate the therapeutic mechanism of ADMSCs transplantation.ResultsThe results showed that after the transplantation of ADMSCs, the liver function of rats was improved, the degree of liver fibrosis and collagen deposition were reduced, and the Hippo signaling pathway was activated. In vitro, ADMSCs can effectively inhibit the proliferation and activation of HSCs induced by TGF-β1 treatment. However, the inhibitory effect of ADMSCs was weakened after blocking the Hippo signaling pathway.ConclusionsADMSCs inhibit HSCs activation by regulating YAP/TAZ, thereby promoting functional recovery after liver fibrosis. These findings lay a foundation for further investigation into the precise mechanism by which ADMSCs alleviate liver fibrosis.

Investigation of Hemorheological Parameters in Ischemic Stroke Patients.

The aim of this study is to determine whether there are any changes in hemorheological parameters, including whole blood viscosity (WBV), plasma viscosity, erythrocyte aggregation, and erythrocyte deformability, in acute ischemic stroke patients, and to establish their relationship with stroke etiology. The study also aims to observe the changes in these parameters, if any, over time and after treatment, and to assess the correlation between risk factors for ischemic stroke and neuroimaging findings. This was a prospective observational study including 70 patients diagnosed with acute ischemic stroke within the first 3 days of the onset of symptoms and 96 healthy controls. Stroke patients were categorized based on TOAST criteria, and hemorheological parameters were measured at admission and on the fifth day post-treatment. Erythrocyte aggregation and deformability were measured using a laser ektacytometer, and viscosity assessment was conducted with a rotational viscometer. Stroke patients exhibited significant differences from the control group in aggregation amplitude, aggregation index, and aggregation half-time (p = 0.001, p = 0.013, p = 0.009, respectively) and showed elevated maximum value of elongation index (p = 0.000). No significant differences in WBV and plasma viscosity were observed between the groups. Post-treatment, the small vessel occlusion subgroup demonstrated a notable reduction in WBV. Additionally, homocysteine levels showed a positive correlation with scattered white matter lesions in basal ganglia and infratentorial regions (p = 0.002, p = 0.039, respectively). Increased predisposition to erythrocyte aggregation may contribute to the occurrence of acute ischemic stroke. Moreover, gaining the ability of erythrocytes to deform and increase blood flow may serve as a compensatory mechanism in the chronic vascular disease process. The risk factors for ischemic stroke may exhibit connections to specific areas within the brain.

European Association for the Study of Obesity (EASO): a new framework for the diagnosis, staging and management of obesity in adults

Obesity is defined as chronic disease process. However, current guidelines for obesity are not aligned sufficiently with those adopted for other chronic diseases. The diagnosis of obesity is based solely on BMI values, not reflecting the role of adipose tissue distribution and function in the severity of the disease. Indications for using the different therapeutic approaches now available for obesity management remain mostly based on anthropometric measurements, rather than on a complete clinical evaluation. This contrast with other chronic diseases, for which therapeutic targets are set, and the choice of the treatment is based on the probability of reaching the target, with adequate and prompt treatment intensification if needed. To stimulate the development of clinical guidelines for obesity more aligned with those already in place for other chronic diseases, the European Association for the Study of Obesity (EASO) conducted a consensus process to propose a new framework for the diagnosis, staging and management of obesity in adults.

Berberine-Loaded PVCL-PVA-PEG Self-Assembled Micelles for the Treatment of Liver Fibrosis.

Liver fibrosis is a necessary pathological process in many chronic liver diseases. Studies have shown that the progression of chronic liver disease can be slowed by rational intervention in hepatic fibrosis. Berberine (BBR), a natural extract of Phellodendron amurense, inhibits the development of liver fibrosis through several mechanisms. However, the clinical application of BBR is limited due to its low solubility. Drug delivery systems have been developed to improve the solubility of hydrophobic drugs and increase their efficacy in treating the liver fibrosis. In this study, a biocompatible nanomicelle was constructed by thin-film dispersion method using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) as a carrier to encapsulate BBR (PVCL-PVA-PEG/BBR-MCs) to improve the solubility of BBR and reduce the systemic side effects. The ability to inhibit HSC-T6 cell activation of PVCL-PVA-PEG/BBR-MCs was evaluated in vitro. The anti-hepatic fibrosis effects of PVCL-PVA-PEG/BBR-MCs were investigated in vivo. PVCL-PVA-PEG/BBR-MCs have a uniform spherical shape with a mean particle size of 60.04 ± 0.027 nm and a potential of 1.49 ± 0.32 mV. It had an encapsulation efficiency of 98.52% ± 0.70 and drug loading content of 6.16% ± 0.04. Compared to free BBR, PVCL-PVA-PEG/BBR-MCs significantly inhibited HSC-T6 cell activation and TGF-β1-induced HSC-T6 cell migration in vitro. In vivo biodistribution experiments showed significantly improved hepatic distribution of PVCL-PVA-PEG/DiD-MCs compared to free DiD, suggesting that PVCL-PVA-PEG micelles enhance the ability of BBR to enter the liver and improve therapeutic efficacy. After treatment, PVCL-PVA-PEG/BBR-MCs significantly improved fibrotic liver structure and reduced collagen deposition in comparison to the CCl4-treated group; the treatment outcome was more effective than that of the free BBR group. Our results demonstrate the advantages of encapsulating BBR in PVCL-PVA-PEG micelles and highlight the potential of PVCL-PVA-PEG/BBR-MCs as a therapeutic strategy for the treatment of liver fibrosis.

Paeoniflorin inhibits PRAS40 interaction with Raptor to activate mTORC1 to reverse excessive autophagy in airway epithelial cells for asthma

BackgroundBronchial asthma is a chronic condition characterized by airway inflammation and remodeling, which pose complex pathophysiological challenges. Autophagy has been identified as a practical strategy to regulate inflammation and remodeling processes in chronic inflammatory diseases with pathological characteristics, such as asthma. PF (Paeoniflorin) is a potential new autophagy regulatory compound. Previous studies have reported that PF can inhibit airway inflammation to alleviate allergic asthma, but whether this is mediated through the regulation of autophagy and the molecular mechanism of action remains unclear. PurposeThe aim of this study was to evaluate the inhibitory effect of natural small molecule PF on asthma by regulating epithelial autophagy. MethodsThe rat asthma model was established through intraperitoneal injection of OVA and aluminum hydroxide suspension, followed by atomized inhalation of OVA for a period of two weeks. Following treatment with PF, histopathology was observed using Masson and H&E staining, while airway Max Rrs was evaluated using a pulmonary function apparatus. Levels of inflammatory cells in BALF were detected using a blood cell analyzer, and levels of inflammatory factors in BALF were detected through Elisa. Expressions of p-PRAS40 and p-Raptor were observed through immunohistochemistry, and levels of Beclin1 and LC3B were observed through immunofluorescence. The structure and quantity of autophagosomes and autophagolysosomal were observed through TEM. An autophagy model of 16HBE cells was established after treatment with 10ng/mL IL13 for 30 minutes. PRAS40 (AKT1S1) overexpression and mutation of PF and Raptor binding site (K207M& L302I& Q417H) were introduced in 16HBE cells. Autophagy in cells was measured by mFRP-GFP-LC3 ADV fluorescent tracer. The binding sites of PF and Raptor were analyzed using the Autodock Tool. The p-mTOR, p-Raptor, p-PRAS40, LC3II/LC3I were detected through Western blot, and interaction between PRAS40-Raptor and Raptor-mTOR was detected through Co-IP. ResultsThe results showed that PF effectively reduced airway inflammation, improved airway pathological changes and remodeling, and maintained lung function. Additionally, PF was found to reverse excessive autophagy in airway epithelial cells. Interestingly, PF activated the mTORC1 subunit PRAS40 and Raptor in airway epithelial cells by regulating their phosphorylation. PRAS40 is an endogenous mTOR inhibitor that promotes autophagy. PF competitively binds Raptor to PRAS40, promoting Raptor-mTOR interactions to activate mTORC1, an outcome that can be reversed by PRAS40 overexpression and site-specific amino acid codon mutations in Raptor. ConclusionThese findings suggest that PF intervention and inhibition of PRAS40-Raptor interaction are effective treatments for bronchial asthma. By activating mTORC1, PF effectively reverses excessive autophagy in airway epithelial cells, leading to improved airway function and reduced inflammation.

How Stem and Progenitor Cells Can Affect Renal Diseases.

Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness.

LncRNA H19 accelerates renal fibrosis by negatively regulating the let-7b-5p/TGF-βR1/COL1A1 axis

BackgroundTransforming growth factor-beta1 (TGF-β1)-mediated renal fibrosis is a critical pathological process of chronic kidney disease worsening to end-stage renal disease. Recent studies have shown that long noncoding RNA H19 (lncRNA H19) is widely involved in the formation and progression of fibrosis in multiple organs. However, its molecular events in renal fibrosis remain to be elucidated. MethodsRats were treated with adenine intragastrically and HK-2 cells were induced by TGF-β1 to construct renal fibrosis models in vivo and in vitro, respectively. Renal histopathological examination was performed using HE and Masson staining. Gene expression levels of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), TGF-β1, fibronectin (Fn), alpha-smooth muscle actin (α-SMA), H19, let-7b-5p, TGF-β receptor 1 (TGF-βR1), and type I collagen (COL1A1) were detected by qRT-PCR. Immunohistochemistry, immunofluorescence, and western blot analysis were used to evaluate the expression of renal fibrosis biomarkers. Dual-luciferase reporter assay was used to verify the presence of binding sites between H19 and let-7b-5p, and between let-7b-5p and TGF-βR1 and COL1A1. ResultsH19 was overexpressed in both in vivo and in vitro renal fibrosis models. H19 knockdown significantly reversed TGF-β1-induced upregulation of fibronectin, COL1A1, and α-SMA and downregulation of E-cadherin in HK-2 cells, accompanied by an increase in let-7b-5p. Let-7b-5p was bound to H19 in HK-2 cells, and its overexpression inhibited TGF-β1-induced HK-2 cell fibrosis. Further experiments determined that let-7b-5p directly targets TGF-βR1 and COL1A1 in HK-2 cells. In addition, inhibition of let-7b-5p reversed the reduction in HK-2 cell fibrosis induced by H19 knockdown. Finally, knockdown of H19 alleviated renal fibrosis in vivo and was associated with regulation of the let-7b-5p/TGF-βR1/COL1A1 axis. ConclusionOur results indicate that knockdown of H19 inhibits renal tubular epithelial fibrosis by negatively regulating the let-7b-5p/TGF-βR1/COL1A1 axis, which may provide new mechanistic insights into CRF progression.

Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor β-mediated mitochondrial malfunction

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor β (GRβ) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRβ ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRβ signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRβ signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Quantitative Magnetic Resonance Imaging (qMRI) of the Small Bowel in Crohn's Disease: State-of-the-Art and Future Directions.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract in which repeated episodes of acute inflammation may lead to long-term bowel damage. Cross-sectional imaging is used in conjunction with endoscopy to diagnose and monitor disease and detect complications. Magnetic resonance imaging (MRI) has demonstrable utility in evaluating inflammatory activity. However, subjective interpretation of conventional MR sequences is limited in its ability to fully phenotype the underlying histopathological processes in chronic disease. In particular, conventional MRI can be confounded by the presence of mural fibrosis and muscle hypertrophy, which can mask or sometimes mimic inflammation. Quantitative MRI (qMRI) methods provide a means to better differentiate mural inflammation from fibrosis and improve quantification of these processes. qMRI may also provide more objective measures of disease activity and enable better tailoring of treatment. Here, we review quantitative MRI methods for imaging the small bowel in CD and consider the path to their clinical translation. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

«I can't imagine it without my nurse»: Experiences of people with chronic kidney disease in the evaluation process as kidney transplant candidates.

This qualitative study aimed to explore the experiences of 11 adults with chronic kidney disease (CKD) undergoing evaluation for kidney transplant (KT) and examine the role played by the nurse in the process. Employing a descriptive phenomenology approach, semi-structured interviews were conducted between October 2022 and July 2023. Thematic analysis, facilitated by Atlas. ti software, revealed a systemic management diagram with "The candidate for kidney transplant and their reality" at the center, followed by "The process of chronic kidney disease and kidney transplantation," and concluding with the most distal category centered on "The kidney transplant access nurse." This organizational framework provided insights into the layers of relationships between emerging themes. The findings underscored the complexity and multidimensionality of the CKD and KT process, emphasizing the nurse's pivotal role as a guide and protector throughout the evaluation process for accessing kidney transplantation. The convergence of results with existing literature highlighted the need to address challenges such as lack of time, resources, and emotional support to enhance the quality of care. Recognizing the nurse's crucial importance in this process, the study emphasizes the significance of addressing these challenges to improve patient care and calls for attention to the nurse's role in guiding individuals through the intricate journey of CKD and kidney transplantation.

Current Concepts, Management, and Outcomes of Traumatic Spinal Cord Injury: A Systematic Review and Meta-analysis

Abstract Background: A spinal cord injury (SCI) is defined as damage to the spinal cord, which may cause temporary or permanent changes in the motor or sensory function. The etiology of SCI can be categorized as either traumatic or non-traumatic. Traumatic SCI is caused by external physical forces, such as motor vehicle accidents, falls, or violent sports-related injuries, which lead to acute spinal cord damage. On the other hand, non-traumatic SCI develops through chronic or acute disease processes, including infections, malignancies, or degenerative pathologies. Materials and Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review focused on surgical outcomes and treatment modalities for traumatic spinal cord injuries. A comprehensive search was performed in the ScienceDirect and PubMed/MEDLINE databases using R software, Rayyan Intelligent Systematic Review, and EXCEL criteria. This review aimed to identify relevant studies and compile data on the treatment and outcomes of traumatic SCI. Results: A total of 38,622 patients with traumatic spinal cord injuries were included in this systematic review. Of these, 19,778 patients were categorized based on neurological deficits: •Complete paraplegia: 1905 patients (9.6%) •Incomplete paraplegia: 402 patients (2%) •Complete tetraplegia: 1417 patients (7.1%) •Incomplete tetraplegia: 550 patients (2.7%) •Death: 45 patients (0.2%) In terms of the level of injury, 18,844 cases were categorized as follows: thoracic injuries: 57%, lumbar injuries: 7.7%, and cervical injuries: 7%. Conclusion: This research emphasizes the importance of adhering to global protocol guidelines for the management of traumatic SCIs. These guidelines can be instrumental in achieving optimal postoperative outcomes across different regions and countries. Given the high incidence of traumatic SCIs, especially from traffic accidents, which result in thousands of injuries and significant loss of life, the implementation of standardized protocols is crucial for improving patient care and minimizing the burden of these injuries.

Mapping the institutionalization of racism in the research about race and traumatic brain injury rehabilitation: implications for Black populations

Purpose Traumatic brain injury (TBI) is a chronic disease process and a public health concern that disproportionately impacts Black populations. While there is an abundance of literature on race and TBI outcomes, there is a lack of scholarship that addresses racism within rehabilitation care, and it remains untheorized. This article aims to illuminate how racism becomes institutionalized in the scientific scholarship that can potentially inform rehabilitation care for persons with TBI and what the implications are, particularly for Black populations. Material and methods Applying Bacchi’s What’s the Problem Represented to be approach, the writings of critical race theory (CRT) are used to examine the research about race and TBI rehabilitation comparable to CRT in other disciplines, including education and legal scholarship. Results A CRT examination illustrates that racism is institutionalized in the research about race and TBI rehabilitation through colourblind ideologies, meritocracy, reinforcement of a deficit perspective, and intersections of race and the property functions of whiteness. A conceptual framework for understanding institutional racism in TBI rehabilitation scholarship is presented. Conclusions The findings from this article speak to the future of TBI rehabilitation research for Black populations, the potential for an anti-racist agenda, and implications for research and practice.