Investigating the causal relationship and potential shared diagnostic genes between primary biliary cholangitis and systemic lupus erythematosus using bidirectional Mendelian randomization and transcriptomic analyses.

Background: The co-occurrence of primary biliary cholangitis (PBC) and systemic lupus erythematosus (SLE) has been consistently reported in observational studies. Nevertheless, the underlying causal correlation between these two conditions still needs to be established. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to assess their causal association. Five MR analysis methods were utilized for causal inference, with inverse-variance weighted (IVW) selected as the primary method. The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and the IVW Radial method were applied to exclude outlying SNPs. To assess the robustness of the MR results, five sensitivity analyses were carried out. Multivariable MR (MVMR) analysis was also employed to evaluate the effect of possible confounders. In addition, we integrated transcriptomic data from PBC and SLE, employing Weighted Gene Co-expression Network Analysis (WGCNA) to explore shared genes between the two diseases. Then, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment methods to perform on the shared genes. The Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was utilized to identify potential shared diagnostic genes. Finally, we verified the potential shared diagnostic genes in peripheral blood mononuclear cells (PBMCs)-specific cell populations of SLE patients by single-cell analysis. Results: Our MR study provided evidence that PBC had a causal relationship with SLE (IVW, OR: 1.347, 95% CI: 1.276 - 1.422, P < 0.001) after removing outliers (MR-PRESSO, rs35464393, rs3771317; IVW Radial, rs11065987, rs12924729, rs3745516). Conversely, SLE also had a causal association with PBC (IVW, OR: 1.225, 95% CI: 1.141 - 1.315, P < 0.001) after outlier correction (MR-PRESSO, rs11065987, rs3763295, rs7774434; IVW Radial, rs2297067). Sensitivity analyses confirmed the robustness of the MR findings. MVMR analysis indicated that body mass index (BMI), smoking and drinking were not confounding factors. Moreover, bioinformatic analysis identified PARP9, ABCA1, CEACAM1, and DDX60L as promising diagnostic biomarkers for PBC and SLE. These four genes are highly expressed in CD14+ monocytes in PBMCs of SLE patients and potentially associated with innate immune responses and immune activation. Conclusion: Our study confirmed the bidirectional causal relationship between PBC and SLE and identified PARP9, ABCA1, CEACAM1, and DDX60L genes as the most potentially shared diagnostic genes between the two diseases, providing insights for the exploration of the underlying mechanisms of these disorders.

TRPA1 promotes cisplatin-induced acute kidney injury via regulating the endoplasmic reticulum stress-mitochondrial damage.

BACKGROUND: Cisplatin is a widely used and effective chemotherapeutic agent against cancer. However, nephrotoxicity is one of the most common side effects of cisplatin, and it can proceed to acute kidney injury (AKI). Studies have reported that activation of transient receptor potential ankyrin-1 (TRPA1) mediates cisplatin-induced renal tubular cytotoxic injury. The aim of this study was to investigate the mechanism of TRPA1 in promoting cisplatin-induced AKI through modulation of the endoplasmic reticulum stress (ERS)-mitochondrial damage. METHODS: A cisplatin-induced HK-2 cell model in vitro and mouse model in vivo were established. The mechanism of TRPA1 promotes AKI was elucidated by H&E staining, TUNEL staining, transmission electron microscope (TEM), immunofluorescence, CCK-8 viability assays, flow cytometry, Western blotting, JC-1 assay, and enzyme linked immunosorbent assay (ELISA). RESULT: In vivo and in vitro, HC-030031 reduced cisplatin-induced Scr and BUN level elevations; improved cisplatin-induced renal tissue injury, apoptosis, and mitochondrial dysfunction; elevated the reduced ERS-associated proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 75 (GRP75), and C/EBP homologous protein (CHOP) levels induced by cisplatin; reduced the elevated optic atrophy 1 (OPA1), mito-fusion 1 (MFN1), and mito-fusion 2 (MFN2) protein levels, and elevated phospho-dynamin-related protein 1 (p-DRP1) and mitochondrial fission factor (MFF) protein levels. HC-030031 also reduced the mitochondria-associated endoplasmic reticulum membrane (MAM) structure. In addition, TRPA1 agonists also decreased cell proliferation, increased apoptosis, and triggered mitochondrial dysfunction and calcium overload in HK-2 cells via modulation of MAM. ERS inhibitors and GRP75 inhibitors reversed these changes caused by TRPA1 agonists. CONCLUSION: Our findings suggest that TRPA1 enhances cisplatin-induced AKI via modulation of ERS and mitochondrial damage.

Design and Implementation of a Highly Efficient Quasi-Cyclic Low-Density Parity-Check Transceiving System Using an Overlapping Decoder.

The traditional LDPC encoding and decoding system is characterized by low throughput and high resource consumption, making it unsuitable for use in cost-efficient, energy-saving sensor networks. Aiming to optimize coding complexity and throughput, this paper proposes a combined design of a novel LDPC code structure and the corresponding overlapping decoding strategies. With regard to structure of LDPC code, a CCSDS-like quasi-cyclic parity check matrix (PCM) with uniform distribution of submatrices is constructed to maximize overlap depth and adapt the parallel decoding. In terms of reception decoding strategies, we use a modified 2-bit Min-Sum algorithm (MSA) that achieves a coding gain of 5 dB at a bit error rate of 10-6 compared to an uncoded BPSK, further mitigating resource consumption, and which only incurs a slight loss compared to the standard MSA. Moreover, a shift-register-based memory scheduling strategy is presented to fully utilize the quasi-cyclic characteristic and shorten the read/write latency. With proper overlap scheduling, the time consumption can be reduced by one third per iteration compared to the non-overlap algorithm. Simulation and implementation results demonstrate that our decoder can achieve a throughput up to 7.76 Gbps at a frequency of 156.25 MHz operating eight iterations, with a two-thirds resource consumption saving.

The levels of bone turnover markers and parathyroid hormone and their relationship in chronic kidney disease.

BACKGROUND: Chronic kidney disease-mineral bone disease (CKD-MBD) is a major complication of CKD. Bone turnover markers (BTMs) are important for clinicians to evaluate and manage patients with CKD-MBD. This study aimed to assess BTMs in patients with CKD and their correlation with parathyroid hormone (PTH) and other clinical characteristics of CKD. METHODS: A total of 408 subjects were included in this study. The serum BTMs including N-terminal midfragment osteocalcin (N-MID OC), ß-isomerized C-terminal telopeptides (ß-CTX), and total procollagen type 1 amino-terminal propeptide (tPINP) were measured. Spearman correlation and multiple stepwise regression models were used to investigate the association of N-MID OC, ß-CTX, and tPINP with the clinical characteristics of CKD patients. RESULTS: BTMs was no significant difference between non-CKD and CKD stages 1, 2, and 3. However, N-MID OC, ß-CTX were significantly increased in patients with CKD stage 4 compared to non-CKD patients and patients with CKD stages 1, 2, and 3. Compared with non-dialysis dependent (NDD)-CKD stage 5, BTMs were significantly higher in dialysis patients. The estimated glomerular filtration rate was negatively associated with N-MID OC (r = -0.479, P < 0.001), ß-CTX (r = -0.474, P < 0.001), and tPINP (r = -0.375, P < 0.001). Multiple analysis showed that N-MID OC (ß = 0.67, P < 0.001), ß-CTX (ß = 0.64, P < 0.001), and tPINP (ß = 0.81, P < 0.001) were independently associated with PTH. CKD patients with secondary hyperparathyroidism (SHPT) have higher ß-CTX (P < 0.05), and N-MID OC (P < 0.05) than patients with non-SHPT. CONCLUSIONS: BTMs in advanced CKD stages were significantly higher than in the early disease stages. PTH level was independently and positively associated with the BTM levels in patients with CKD. In the advanced stage of CKD, ß-CTX and N-MID OC levels were significantly higher in those with SHPT than those with non-SHPT.

Dipeptidyl-peptidase-4 inhibitors have anti-inflammatory effects in patients with type 2 diabetes.

AIMS: Systematic low-grade inflammation is considered to be an important factor leading to the development of T2DM and the progression of its complications. Dipeptidyl-peptidase-4 (DPP-4) inhibitors show potential anti-inflammatory effects in patients with T2DM. This meta-analysis aimed to evaluate the anti-inflammatory effects of DPP-4 inhibitors in patients with T2DM. METHODS: A comprehensive search was performed in PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials that assess the anti-inflammatory effects of DPP-4 inhibitors. Quantitative data analysis was conducted by a random-effects model. Sensitivity analyses were conducted to determine the robustness of the pooled results. RESULTS: Twenty-two studies with 1595 patients with T2DM were included. Pooled results showed that DPP-4 inhibitor therapy was significantly associated with the reduction of C-reactive protein (CRP) (SMD, - 0.56, p < 0.01), TNF-α (SMD, - 1.69, p < 0.01), IL-6 (SMD, - 0.67, p < 0.01), and IL-1ß (WMD, - 8.21 pg/ml, p < 0.01). Leave-one-out meta-analysis showed no significant change in the pooled results of CRP and TNF-α. CONCLUSION: This meta-analysis demonstrated that DPP-4 inhibitors can significantly attenuate low-grade inflammatory state in patients with T2DM. In addition to improving glycemic control, DDP-4 inhibitors might offer extra therapeutic value by controlling inflammation.

Biopsy-proven granulomatous interstitial nephritis associated with vancomycin in an adult patient: a case report.

Acute kidney injury (AKI) caused by vancomycin mainly manifests as acute interstitial nephritis or acute tubular necrosis. Here, the rare case of a 71-year-old female patient with no history of kidney disease, who was diagnosed with granulomatous interstitial nephritis associated with vancomycin, is reported. The patient had been treated with vancomycin for over a month for an abscess in her right thigh. She presented to the emergency department with a history of fever, scattered rash, oliguria and elevated serum creatinine for >10 days. After hospitalization, the vancomycin trough concentration was confirmed to be >50 µg/ml. The patient received furosemide and continuous renal replacement therapy for AKI, teicoplanin and piperacillin/tazobactam for pulmonary infection, and urapidil, sodium nitroprusside and nifedipine for elevated blood pressure. Percutaneous ultrasound-guided kidney biopsy was performed. Light microscopy revealed granuloma formation, and diffuse infiltration of lymphocytes, monocytes, eosinophils, and some multinucleated giant cells. Finally, the patient was diagnosed with vancomycin-induced granulomatous interstitial nephritis and was treated with high-flux haemodialysis and 16 mg oral methylprednisolone, daily, for 3 weeks, which contributed to a significant recovery of renal function. This case suggests the need for regular vancomycin concentration testing during treatment. When AKI due to vancomycin occurs, a renal biopsy may be performed to help diagnose and treat the condition.

A case report: Catatonic symptoms secondary to systemic lupus erythematosus with multiple infections: neuropsychiatric or "mimickers?"

RATIONALE: Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) manifestations. However, typical symptoms of catatonia are uncommon. Neuropsychiatric SLE or its "mimickers" may cause NP symptoms, making differential diagnosis a significant challenge in clinical practice. PATIENT CONCERNS: A 68-year-old female with SLE was hospitalized for edema, lung infection, and recurrent fungal mouth ulcers after multiple courses of cortisol and immunosuppressive therapy. Five days after admission, stupor, immobility, mutism, and rigidity were observed. DIAGNOSIS: "Mimickers": catatonic disorder due to a general medical condition. INTERVENTION: Initially, relevant laboratory tests, imaging studies, and the disease activity index score were performed. A survey of the causes of the disease was conducted among the patient's relatives. Subsequently, we discontinued moxifloxacin, corticosteroids, fluconazole, and other medications and inserted a gastric tube for nutritional support. During this process, traditional Chinese medicine and acupuncture have been utilized. OUTCOMES: After 3 days, the patient recovered and only complained of fatigue. CONCLUSION: When SLE presents with NP symptoms, it is essential to make a correct diagnosis in order to guide appropriate treatment by actively searching for inducers and clinical, laboratory, and neuroradiological characteristics that can aid in the differential diagnosis. When treatment options are limited, it can be beneficial to try a variety of combination strategies, such as traditional Chinese medicine and acupuncture.

Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide and is a significant burden on healthcare systems. α-klotho (klotho) is a protein known for its anti-aging properties and has been shown to delay the onset of age-related diseases. Soluble klotho is produced by cleavage of the full-length transmembrane protein by a disintegrin and metalloproteases, and it exerts various physiological effects by circulating throughout the body. In type 2 diabetes and its complications DN, a significant decrease in klotho expression has been observed. This reduction in klotho levels may indicate the progression of DN and suggest that klotho may be involved in multiple pathological mechanisms that contribute to the onset and development of DN. This article examines the potential of soluble klotho as a therapeutic agent for DN, with a focus on its ability to impact multiple pathways. These pathways include anti-inflammatory and oxidative stress, anti-fibrotic, endothelial protection, prevention of vascular calcification, regulation of metabolism, maintenance of calcium and phosphate homeostasis, and regulation of cell fate through modulation of autophagy, apoptosis, and pyroptosis pathways. Diabetic retinopathy shares similar pathological mechanisms with DN, and targeting klotho may offer new insights into the prevention and treatment of both conditions. Finally, this review assesses the potential of various drugs used in clinical practice to modulate klotho levels through different mechanisms and their potential to improve DN by impacting klotho levels.

Severe varicella-zoster virus meningoencephalomyelitis coexisting with visceral disseminated varicella-zoster virus infection in a patient with lupus nephritis: A case report.

RATIONALE: Meningoencephalomyelitis and visceral dissemination infection are rare but life-threatening complications of either the primary infection or reactivation of varicella-zoster virus (VZV) in immunocompromised patients. To date, few studies have reported the co-existence of VZV meningoencephalomyelitis and the visceral dissemination of VZV infection. PATIENT CONCERNS: A 23-year-old male was diagnosed with lupus nephritis class III and was being treated with oral prednisone and tacrolimus. The patient exhibited herpes zoster 21-day after the initiation of therapy and experienced unbearable abdominal pain and generalized seizures 11 days after the onset of a zoster rash. Magnetic resonance imaging showed progressive lesions in the cerebrum, brainstem, and cerebellum, as well as meningeal thickening and thoracic myelitis. Computed tomography showed pulmonary interstitial infiltration, partial intestinal dilatation, and effusion. Metagenomic next-generation sequencing revealed 198,269 and 152,222 VZV-specific reads in the cerebrospinal fluid and bronchoalveolar lavage fluid, respectively. DIAGNOSES: Based on the clinical and genetic findings, this patient was finally diagnosed with VZV meningoencephalomyelitis and visceral disseminated VZV infection. INTERVENTIONS: The patient received intravenous acyclovir (0.5 g every 8 hours) combined with plasma exchange and intravenous immunoglobulin. Treatment against secondary bacterial and fungal infections, organ support therapy and rehabilitation training were given simultaneously. OUTCOME: The patient's peripheral muscle strength did not improve and repeated metagenomic next-generation sequencing showed the persistence of VZV-specific reads in the cerebrospinal fluid. The patient finally abandoned therapy due to financial constraints at the 1-month follow-up. LESSONS: Patients with autoimmune diseases receiving immunosuppressive therapy should be warned about the possibility of developing serious neurological infections and visceral disseminated VZV infections as side effects. Early diagnosis and the early initiation of intravenous acyclovir therapy are important for such cases.

Bacillus subtilis reduces antibiotic resistance genes of animal sludge in vermicomposting by improving heat stress tolerance of Eisenia foetida and bacterial community adjustment.

Antibiotic resistance genes (ARGs) in livestock industry have been recognized as a kind of pollutant. The effect of Bacillus subtilis (B. subtilis) as an additive for the reduction of ARGs in animal sludge from livestock and poultry wastewater treatment plant during vermicomposting was investigated. We also evaluated the oxidative stress level and growth of earthworms, Eisenia foetida, bacterial community succession, and the quality of the end products. Two treatments were conducted using B. subtilis, one at 18 °C and another at 28 °C. Controls were setup without the bacteria. The results showed that inoculation of B. subtilis promoted the degradation of organics at 28 °C and increased the germination index to 236%. The increased activities of the superoxide dismutase (1.69 U/mg pr) and catalase (8.05 U/mg pr) and the decreased activity of malondialdehyde (0.02 nmol/mg pr) by B. subtilis at 28 °C showed that the earthworms were relieved of heat stress. The addition of B. subtilis reduced the abundance of 32 target ARGs, including integron (intI-1), transposase (IS613) and resistant genes, such as sulfonamide (sul2), quinolone (oprJ), macrolide-lincosamide-streptogramin group B (ermF, ermB), tetracycline (tetL-02, tetX), ß-lactama (blaOXA10-01) and aminoglycoside [strB, aac(6')-Ib(aka aacA4)-01, aac(6')-Ib(aka aacA4)-02]. Organic matter degrading Membranicola, Paludisphaera, Sphingorhabdus and uncultured bacterium belonging to the order Chitinophagales, nitrifying and nitrogen-fixing Singulisphaera and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, soil remediating Achromobacter, and plant growth promoting Kaistia, Galbibacter and Ilumatobacter were increased significantly (P < 0.05). However, the growth of harmful bacteria such as Burkholderiaceae was inhibited in the vermicompost. In earthworm guts, the probiotic Mesorhizobium was promoted, while the pathogenic uncultured bacterium belonging to the family Enterobacteriaceae was reduced. Besides, B. subtilis enhanced the host relationships between bacteria and ARGs. These findings might be helpful in the removal of ARGs in animal wastes and in understanding the synergy between earthworms and microorganisms.

Effects of vitamin D on inflammatory state in patients with chronic kidney disease: A controversial issue.

BACKGROUND: The anti-inflammatory effect of vitamin D in patients with chronic kidney disease (CKD) remains controversial. This study aimed to conduct a meta-analysis of randomized controlled trials to assess the anti-inflammatory effects of vitamin D in patients with CKD. METHODS: We searched Embase, Science Citation Index, Medline, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries for randomized controlled trials that comparing vitamin D with control groups for inflammatory markers in patients with CKD. Subgroup analysis was performed based on treatment duration (short-term treatment, long-term treatment), type of patients (predialysis CKD, dialysis, kidney transplant), 25(OH)D levels (25(OH)D deficiency or normal 25(OH)D), and methods of C-reactive protein (CRP) test (standard CRP test or high-sensitivity CRP [hs-CRP] test). RESULTS: Eighteen trials with 1834 patients were included in the present study. There were no significant differences between the vitamin D group and control group for CRP (WMD, -0.3 mg/L; 95% CI, -0.81 to 0.22, p = 0.26, I2  = 62%), interleukin-6 (IL-6) (WMD, -1.07 pg/ml; 95% CI, -2.44 to 0.30, p = 0.12, I2  = 52%), and tumor necrosis factor-α (TNF-α) (WMD, -0.00 pg/ml; 95% CI, -0.36 to 0.35, p = 0.99, I2  = 0%) in patients with CKD. Subgroup analysis showed vitamin D can improve hs-CRP, but not CRP. The rest of subgroups showed that no significant differences were observed between the vitamin D group and control group based on 25(OH)D levels, treatment duration, and predialysis CKD or dialysis patients. CONCLUSION: This meta-analysis demonstrates that vitamin D supplementation does not have anti-inflammatory effects in CKD patients. Well-designed randomized controlled trials with large samples are required to confirm this conclusion. It is still needed to find an effective treatment for inflammatory state in CKD.

Statins Have an Anti-Inflammation in CKD Patients: A Meta-Analysis of Randomized Trials.

Background: Persistent inflammation has been recognized as an important comorbid condition in patients with chronic kidney disease (CKD) and is associated with many complications, mortality, and progression of CKD. Previous studies have not drawn a clear conclusion about the anti-inflammatory effects of statins in CKD. This meta-analysis is aimed at assessing the anti-inflammatory effects of statins therapy in patients with CKD. Methods: A comprehensive literature search was conducted in these databases (Medline, Embase, Cochrane library, and clinical trials) to identify the randomized controlled trials that assess the anti-inflammatory effects of statins. Subgroup, sensitivity, and trim-and-fill analysis were conducted to determine the robustness of pooled results of the primary outcome. Results: 25 eligible studies with 7921 participants were included in this meta-analysis. The present study showed that statins therapy was associated with a decreased C-reactive protein (CRP) (-2.06 mg/L; 95% CI: -2.85 to -1.27, p < 0.01). Subgroup, sensitivity, and trim-and-fill analysis showed that the pooled results of CPR were stable. Conclusion: This meta-analysis demonstrates that statins supplementation has anti-inflammatory effects in patients with CKD. Statins exert an anti-inflammatory effect that is clinically important in improving complications, reducing mortality, and slowing progression in CKD. We believe that the benefits of statins to CKD are partly due to their anti-inflammatory effects. However, stains usually are prescribed in the CKD patients with dyslipidemia, whether statins can reduce inflammation in CKD patients with normal serum lipid needed to explore in the future. Therefore, we suggest that randomized clinical trials need to assess the effect of statins in CKD patients with normal serum lipid. Whether statins can be prescribed for aiming to inhibit inflammation in CKD also needed further study. Trial Registration. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42022310334.

Association of Exercise With Vascular Function in Patients With CKD: A Meta-Analysis of Randomized Controlled Trials.

Background and Aim: Vascular function is associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Whether exercise improves vascular function in such patients remains controversial. This study aimed to conduct a meta-analysis on the effect of exercise training on the vascular function of patients with CKD. Methods: Embase, the Cochrane Central Register of Controlled Trials, and Medline were searched from inception until November 15, 2021. The terms exercise, CKD, dialysis, kidney transplant, and randomized controlled trial (RCT) were searched alone or in combination. RCTs were included when studies compared exercise with active control, usual care, or no intervention, and the studies reported vascular function on patients with CKD. Results: This meta-analysis included 18 RCTs with 817 patients. Exercise training was significantly associated with decreased pulse wave velocity weighted mean difference (WMD), -0.56; 95% confidence interval (CI), -1.02 to -0.09, P = 0.02 and augmentation index (WMD, -3.26; 95% CI, -5.46 to -1.05, P = 0.004). It was also significantly associated with improved peak VO2 (WMD, 2.64; 95% CI, 1.94-3.35, P < 0.00001), general health (WMD, 7.03; 95% CI, 0.65-13.42, P = 0.03), and vitality (WMD, 9.1; 95% CI, 2.50-15.69, P = 0.007). Conclusions: The meta-analysis suggested that exercise training improved vascular function in patients with CKD. An exercise program should be considered as one of the management strategies for vascular dysfunction in patients with CKD. Further studies are needed to demonstrate that exercise training improves cardiovascular diseases in patients with CKD.

Influence of different inoculation densities of black soldier fly larvae (Hermetia illucens) on heavy metal immobilization in swine manure.

The disposal of organic waste by the biocomposting of black soldier fly larvae (BSFL) has drawn broad attention. However, the discrepancies in heavy metal immobilization between BSFL biocomposting with different inoculation densities and aerobic composting need to be further researched. In this study, BSFL with inoculation densities of 0.08%, 0.24% and 0.40% was added to swine manure to investigate its influence on heavy metal bioaccumulation and bioavailability. The physicochemical properties, BSFL growth performance and amino acid contents were measured. The results showed that the germination index, total prepupal yield and bioavailable fraction removal rate (%) of Cr and Pb at an inoculation density of 0.40% of BSFL were the highest among all of the BSFL biocomposting groups. Although the bioaccumulation factor and heavy metal (Cd, Cr, Cu and Zn) concentrations of the BSFL body from swine manure with inoculation densities of 0.24% and 0.40% of BSFL were similar, the BSFL inoculation density of 0.40% had the best absorption effect on these heavy metals in terms of total prepupal yield. Therefore, this study provides a basis for exploring the optimal inoculation density of BSFL biocomposting to reduce the harmful effects of heavy metals in swine manure.

Emodin-Mediated Treatment of Acute Kidney Injury.

Acute kidney injury (AKI), a common condition associated with a high mortality rate, is characterized by declined glomerular filtration rate, retention of nitrogen products, and disturbances in balance of water, electrolyte, and acid-base. Up to date, there is no effective treatment for AKI. Despite the continuous improvement in blood purification techniques, a considerable proportion of patients with AKI still progress to end-stage renal disease. These patients with advanced stage of end-stage renal disease will require long-term renal replacement therapy, which places a heavy burden on the family and the society. In recent years, the use of traditional Chinese medicine (TCM) in AKI management has been gradually increasing. Clinical evidence has demonstrated that three-month treatment with TCM produced better clinical outcomes in terms of clinical effectiveness rate and improvement in renal function (serum creatinine, neutrophil gelatinase-associated lipocalin, and cystatin C) compared with Western medicine. Rhubarb is a commonly used herb in TCM for the treatment of AKI. The main active component of rhubarb is emodin, which was first recorded in Shennong's Classic of Materia Medica. It has been shown that emodin has a variety of pharmacological activities including antibacterial, anti-inflammatory, antiulcer, and immunosuppressive effects. Emodin has been found to be effective against renal fibrosis and has been widely studied for its effects on kidney diseases such as diabetic nephropathy, renal fibrosis, and AKI. Moreover, promising results have been obtained from these studies. In this study, the results obtained from research on the use of emodin for AKI treatment has been reviewed.

TRPA1 promotes cisplatin-induced nephrotoxicity through inflammation mediated by the MAPK/NF-κB signaling pathway.

BACKGROUND: The nephrotoxicity induced by cisplatin (DDP) has been a severe obstacle for its clinical use in anticancer treatment. The apoptosis and inflammation induced by DDP are the main causes of the nephrotoxicity. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation ligand-gated channel that is involved in the inflammation progress. METHODS: The apoptosis, inflammation, MAPK/NF-κB signaling pathway, and TRPA1 expression were assessed after HEK293 cells had been induced by DDP, and the role of TRPA1 in apoptosis and inflammation of DDP-induced HEK293 cells treated with TRPA1 antagonist HC-030031 was also evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), flow cytometry, and western blot assays. RESULTS: The cell viability was reduced by DDP in both a time-dependent and dose-dependent manner with a minimal cytotoxic concentration of 10 µM. Moreover, DDP induced an enhancement of the apoptosis and inflammation in a dose-dependent manner, as indicated by the increase of the relative protein level of cleaved-caspase3 (cleaved-cas3), the cleavage product of caspase-3 substrate poly-ADP-ribose polymerase (cleaved-PARP) and inducible nitric oxide synthase (iNOS), and the messenger RNA (mRNA) expression level of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ). Additionally, DDP treatment increased the protein phosphorylation expression of IKKß, JNK, ERK, and p38 in a dose-dependent manner, which was antagonized by the treatment of NF-κB-specific inhibitor BAY 11-7082 and pan-MAPK inhibitor U0126. It was also found that DDP upregulated the expression of TRPA1 at both the mRNA and protein levels in a dose-dependent manner. Besides, block of TRPA1 with HC-030031 relieved the apoptosis, diminished the level of IL-1ß, IL-6, TNF-α, and INF-γ, reduced the level of cleaved-cas3, cleaved-PARP, and iNOS, decreased the p-IKKß, p-JNK, p-ERK, and p-p38 expression, and enhanced the expression of IκBα. CONCLUSIONS: Taken together, these results indicate that TRPA1 regulates DDP-induced nephrotoxicity via inflammation mediated by the MAPK/NF-κB signaling pathway in HEK293 cells.

Madelung's disease with alcoholic liver disease and acute kidney injury: A case report.

BACKGROUND: Madelung's disease (MD) is a rare disorder of lipid metabolism, characterized by the growth of unencapsulated masses of adipose tissue symmetrically deposited around the neck, shoulders, or other sites around the body. Its pathological mechanism is not yet known. One of the most common comorbidities in MD patients is liver disease, especially chronic alcoholic liver disease (CALD); however, no reports exist of acute kidney injury (AKI) with MD. CASE SUMMARY: We report a 60-year-old man who presented with complaint of edema in the lower limbs that had persisted for 3 d. Physical examination showed subcutaneous masses around the neck, and history-taking revealed the masses to have been present for 2 years and long-term heavy drinking. Considering the clinical symptoms, along with various laboratory test results and imaging characteristics, a diagnosis was made of MD with acute exacerbation of CALD and AKI. The patient was treated with liver function protection and traditional Chinese medicine, without surgical intervention. He was advised to quit drinking. After 10 d, the edema had subsided, renal function indicators returned to normal, liver function significantly improved, and size of subcutaneous masses remained stable. CONCLUSION: In MD, concomitant liver or kidney complications are possible and monitoring of liver and kidney functions can be beneficial.

Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.

OBJECTIVES: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. METHODS: GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. RESULTS: There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. CONCLUSIONS: We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.

Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. MATERIALS AND METHODS: In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. RESULTS: Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. CONCLUSIONS: Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.