Curcumin ameliorates focal segmental glomerulosclerosis by inhibiting apoptosis and oxidative stress in podocytes.

Focal segmental glomerulosclerosis (FSGS), a podocyte disease, is the leading cause of end-stage renal disease (ESRD). Nevertheless, the current effective treatment for FSGS is deficient. Curcumin (CUR) is a principal curcuminoid of turmeric, which is a member of the ginger family. Previous studies have shown that CUR has renoprotective effects. However, the mechanism of CUR in anti-FSGS is not clear. This study aimed to explore the mechanism of CUR against FSGS through a combination of network pharmacological methods and verification of experiments. The analysis identified 98 shared targets of CUR against FSGS, and these 98 targets formed a network of protein-protein interactions (PPI). Of these 98 targets, AKT1, TNF, IL-6, VEGFA, STAT3, MAPK3, HIF1A, CASP3, IL1B, and JUN were identified as the hub targets. Molecular docking suggested that the best binding to CUR is MAPK3 and AKT1. Apoptotic process and cell proliferation were identified as the main biological processes of CUR against FSGS by gene ontology (GO) analysis. The most enriched signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was the PI3K-AKT signaling pathway. Western blots and flow cytometry showed that CUR could inhibit adriamycin (ADR) induced apoptosis, oxidative stress damage, and attenuate podocyte epithelial-mesenchymal transition (EMT) by repressing the AKT signaling pathway. Collectively, our study demonstrates that CUR can attenuate apoptosis, oxidative stress damage, and EMT in FSGS in vitro. These results supply a compelling basis for future studies of CUR for the clinical treatment of FSGS.

Lack of serum- and glucocorticoid-inducible kinase 3 leads to podocyte dysfunction.

Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)-mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN. Adriamycin (ADR)-treated mice developed proteinuria and had decreased renal glomerular SGK3 expression in comparison to control mice. Consistent with a role for SGK3 in the ADR effect, SGK3 knockout (KO) mice had markedly reduced kidney podocin expression and significantly elevated proteinuria compared with wild-type mice. Electron microscopy revealed that SGK3 KO mice displayed partial effacement of podocyte foot processes. Further, a SGK3 target protein, glycogen synthase kinase-3 (GSK3), was discovered to be dramatically activated in PAN and SGK3 shRNA-treated MPCs and in SGK3 KO mice. Taken together, these data strongly suggest that SGK3 plays a significant role in regulating podocyte function, likely by controlling the expression and activity of GSK3.-Peng, L.-Q., Zhao, H., Liu, S., Yuan, Y.-P., Yuan, C.-Y., Mwamunyi, M.-J., Pearce, D., Yao, L.-J. Lack of serum- and glucocorticoid-inducible kinase 3 leads to podocyte dysfunction.

[NIR spectroscopy combined with stability and equivalence MW-PLS method applied to analysis of hyperlipidemia indexes].

UNLABELLED: Moving window partial least square (MW-PLS) method was improved by considering the stability and equivalence, and was used for the wavelength optimization of reagent-free near-infrared (NIR) spectroscopic analysis of total cholesterol (TC) and triglycerides (TG) for hyperlipidemia. A random and stability-dependent framework of calibration, prediction, and validation was proposed. From all human serum samples (negative 145 and positive 158, a total of 303 sample), 103 samples (negative 44 and positive 59) were randomly selected for the validation set, the remaining samples (negative 101 and positive 99, a total of 200 sample) were used as modeling set; then the modeling set was randomly divided into calibration set (negative 51 and positive 49, a total of 100 sample) and prediction set (negative 50 and positive 50, a total of 100 sample) by 50 times. To produce modeling stability, the model parameters were optimized based on the average prediction effect for all divisions; the optimized models were validated by using the validation samples. The obtained optimal MW-PLS wavebands were 1,556~1,852 nm for TC and 1,542-1,866 nm for TG. In order to solve the problem that instrument design typically involves some limitations of position and number of wavelengths because of cost and material properties, the equivalent model sets were proposed, and a unique public waveband 1,542-1,852 nm of the equivalent model sets for TC, TG was found. The validation results show that: using the optimal MW-PLS wavebands, validation samples' root mean square error of prediction (V SEP) for TC, TG were 0.177, 0.100 mmol · L(-1), the correlation coefficient of prediction (V_Rp) for TC, TG were 0.988, 0.996, and the sensitivity and specificity for hyperlipidemia achieved 95.0%, 90.5%, respectively; using the public equivalent wavebands, the V_SEP for TC, TG were 0.177, 0.101 mmol · L(-1)), the V_Rp for TC, TG were 0.988, 0.996, and the sensitivity and specificity achieved 92.7%, 90.3%, respectively. CONCLUSION: NIR spectroscopy combined with the stability and equivalenceimprovement MW-PLS method can provide a potential tool for detecting hyperlipidemia for large population.

Macrophage-Targeting DNA Nanomaterials: A Future Direction of Biological Therapy.

DNA can be used for precise construction of complex and flexible micro-nanostructures, including DNA origami, frame nucleic acids, and DNA hydrogels. DNA nanomaterials have good biocompatibility and can enter macrophages via scavenger receptor-mediated endocytosis. DNA nanomaterials can be uniquely and flexibly designed to ensure efficient uptake by macrophages, which represents a novel strategy to regulate macrophage function. With the development of nanotechnology, major advances have been made in the design and manufacturing of DNA nanomaterials for clinical therapy. In diseases accompanied by macrophage disturbances including tumor, infectious diseases, arthritis, fibrosis, acute lung injury, and atherosclerosis, DNA nanomaterials received considerable attention as potential treatments. However, we lack sufficient information to guarantee precise targeting of macrophages by DNA nanomaterials, which precludes their therapeutic applications. In this review, we summarize recent studies of macrophage-targeting DNA nanomaterials and discuss the limitations and challenges of this approach with regard to its potential use as a biological therapy.

Redox TRPs in Ischemia-Reperfusion Injury and Their Pharmacological Value.

Ischemia-reperfusion injury (IRI) is a complex phenomenon. Although researchers have long been aware of IRI, its complex signaling events and potential therapeutic targets are still an active research area. The role of reactive oxygen species in IRI has garnered great interest among scientists. Recent studies have found that reactive oxygen species produced by IRI can activate redox-sensitive transient receptor potential channels (redox TRPs). The discovery of redox TRPs provides a new perspective for understanding the mechanism of IRI.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.

BACKGROUND: Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies. AIM: To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function. METHODS: Clinical data from patients with liver cancer admitted to Suzhou Ninth People's Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups. RESULTS: One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 µmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4+ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8+ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4+/CD8+ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups. CONCLUSION: The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.

SGK3 promotes vascular calcification via Pit-1 in chronic kidney disease.

Rationale: Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia. However, the regulation of VC remains unclear despite extensive research. Although serum- and glucocorticoid-induced kinase 3 (SGK3) regulate the sodium-dependent phosphate cotransporters in the intestine and kidney, its effect on VC in CKD remains unknown. Additionally, type III sodium-dependent phosphate cotransporter-1 (Pit-1) plays a significant role in VC development induced by high phosphate in vascular smooth muscle cells (VSMCs). However, it remains unclear whether SGK3 regulates Pit-1 and how exactly SGK3 promotes VC in CKD via Pit-1 at the molecular level. Thus, we investigated the role of SGK3 in the certified outflow vein of arteriovenous fistulas (AVF) and aortas of uremic mice. Methods and Results: In our study, using uremic mice, we observed a significant upregulation of SGK3 and calcium deposition in certified outflow veins of the AVF and aortas, and the increase expression of SGK3 was positively correlated with calcium deposition in uremic aortas. In vitro, the downregulation of SGK3 reversed VSMCs calcification and phenotype switching induced by high phosphate. Mechanistically, SGK3 activation enhanced the mRNA transcription of Pit-1 through NF-κB, downregulated the ubiquitin-proteasome mediated degradation of Pit-1 via inhibiting the activity of neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2), an E3 ubiquitin ligase. Moreover, under high phosphate stimulation, the enhanced phosphate uptake induced by SGK3 activation was independent of the increased protein expression of Pit-1. Our co-immunoprecipitation and in vitro kinase assays confirmed that SGK3 interacts with Pit-1 through Thr468 in loop7, leading to enhanced phosphate uptake. Conclusion: Thus, it is justifiable to conclude that SGK3 promotes VC in CKD by enhancing the expression and activities of Pit-1, which indicate that SGK3 could be a therapeutic target for VC in CKD.

The Physiopathologic Roles of Calcium Signaling in Podocytes.

Calcium (Ca2+) plays a critical role in podocyte function. The Ca2+-sensitive receptors on the cell surface can sense changes in Ca2+ concentration, and Ca2+ flow into podocytes, after activation of Ca2+ channels (such as transient receptor potential canonical (TRPC) channels and N-type calcium channels) by different stimuli. In addition, the type 2 ryanodine receptor (RyR2) and the voltage-dependent anion channel 1 (VDAC1) on mitochondrial store-operated calcium channels (SOCs) on the endoplasmic reticulum maintain the Ca2+ homeostasis of the organelle. Ca2+ signaling is transmitted through multiple downstream signaling pathways and participates in the morphogenesis, structural maintenance, and survival of podocytes. When Ca2+ is dysregulated, it leads to the occurrence and progression of various diseases, such as focal segmental glomerulosclerosis, diabetic kidney disease, lupus nephritis, transplant glomerulopathy, and hypertensive renal injury. Ca2+ signaling is a promising therapeutic target for podocyte-related diseases. This review first summarizes the role of Ca2+ sensing, Ca2+ channels, and different Ca2+-signaling pathways in the biological functions of podocytes, then, explores the status of Ca2+ signaling in different podocyte-related diseases and its advances as a therapeutic target.

Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases.

SLIT ligand and its receptor ROBO were initially recognized for their role in axon guidance in central nervous system development. In recent years, as research has advanced, the role of the SLIT-ROBO signaling pathway has gradually expanded from axonal repulsion to cell migration, tumor development, angiogenesis, and bone metabolism. As a secreted protein, SLIT regulates various pathophysiological processes in the kidney, such as proinflammatory responses and fibrosis progression. Many studies have shown that SLIT-ROBO is extensively involved in various aspects of kidney development and maintenance of structure and function. The SLIT-ROBO signaling pathway also plays an important role in different types of kidney disease. This article reviews the advances in the study of the SLIT-ROBO pathway in various renal pathophysiological and kidney disorders and proposes new directions for further research in this field.

PKCα regulates vasopressin-induced aquaporin-2 trafficking in mouse kidney collecting duct cells in vitro via altering microtubule assembly.

AIM: Aquaporin-2 (AQP2) is a vasopressin-regulated water channel located in the collecting tubule and collecting duct cells of mammalian kidney. The aim of this study is to investigate whether PKCα plays a role in vasopressin-induced AQP2 trafficking in mouse inner medullary collecting duct 3 (mIMCD3) cells. METHODS: AQP2-mIMCD3 stable cell line was constructed by transfection of mouse inner medullary collecting duct 3 (mIMCD3) cells with AQP2-GFP construct. Then the cells were transfected with PKCα shRNA, PKCα A/25E, or PKCα scrambled shRNA. The expression levels of PKCα, AQP2, and phospho-S256-AQP2 were analyzed using Western blot. The interaction between AQP2 and PKCα was examined using immunoprecipitation. The distribution of AQP2 and microtubules was studied using immunocytochemistry. The AQP2 trafficking was examined using the biotinylation of surface membranes. RESULTS: Treatment of AQP2-mIMCD3 cells with 100 µmol/L of 1-desamino-8-D-arginine vasopressin (DdAVP) for 30 min stimulated the translocation of AQP2 from the cytoplasm to plasma membrane through influencing the microtubule assembly. Upregulation of active PKCα by transfection with PKCα A/25E plasmids resulted in de-polymerization of α-tubulin and redistributed AQP2 in the cytoplasm. Down-regulation of PKCα by PKCα shRNA partially inhibited DdAVP-stimulated AQP2 trafficking without altering α-tubulin distribution. Although 100 µmol/L of DdAVP increased AQP2 phosphorylation at serine 256, down-regulation of PKCα by PKCα shRNA did not influence DdAVP-induced AQP2 phosphorylation, suggesting that AQP2 phosphorylation at serine 256 was independent of PKCα. Moreover, PKCα did not physically interact with AQP2 in the presence or absence of DdAVP. CONCLUSION: Our results suggested that PKCα regulates AQP2 trafficking induced by DdAVP via microtubule assembly.

Contributions of SGK3 to transporter-related diseases.

Serum- and glucocorticoid-induced kinase 3 (SGK3), which is ubiquitously expressed in mammals, is regulated by estrogens and androgens. SGK3 is activated by insulin and growth factors through signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 can activate ion channels (TRPV5/6, SOC, Kv1.3, Kv1.5, Kv7.1, BKCa, Kir2.1, Kir2.2, ENaC, Nav1.5, ClC-2, and ClC Ka), carriers and receptors (Npt2a, Npt2b, NHE3, GluR1, GluR6, SN1, EAAT1, EAAT2, EAAT4, EAAT5, SGLT1, SLC1A5, SLC6A19, SLC6A8, and NaDC1), and Na+/K+-ATPase, promoting the transportation of calcium, phosphorus, sodium, glucose, and neutral amino acids in the kidney and intestine, the absorption of potassium and neutral amino acids in the renal tubules, the transportation of glutamate and glutamine in the nervous system, and the transportation of creatine. SGK3-sensitive transporters contribute to a variety of physiological and pathophysiological processes, such as maintaining calcium and phosphorus homeostasis, hydro-salinity balance and acid-base balance, cell proliferation, muscle action potential, cardiac and neural electrophysiological disturbances, bone density, intestinal nutrition absorption, immune function, and multiple substance metabolism. These processes are related to kidney stones, hypophosphorous rickets, multiple syndromes, arrhythmia, hypertension, heart failure, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, glaucoma, ataxia idiopathic deafness, and other diseases.

TOPK Activation Exerts Protective Effects on Cisplatin-induced Acute Kidney Injury.

OBJECTIVE: T-LAK-cell-originated protein kinase (TOPK), a PSD95-Disc large-ZO1 (PDZ) binding kinase (PBK), is a novel member of the mitogen-activated protein kinase (MAPK) family. Studies have shown that TOPK plays a critical role in the function of tumor cells, including apoptosis and mitosis. However, little is known on the effect of TOPK in cisplatin-induced acute kidney injury (CP-AKI). This study aimed to investigate the role and mechanism of TOPK in CP-AKI. METHODS: Cisplatin was administered to C57BL/6 mice and cultured kidney tubular epithelial cells (TECs) to establish the CP-AKI murine or cellular models. TECs were then stimulated with the specific inhibitor of TOPK OTS514 or transfected with the recombinant-activated plasmid TOPK-T9E to inhibit or activate TOPK. The TECs were treated with AKT inhibitor VIII following stimulation with OTS514 or cisplatin. Western blotting and flow cytometry were used to evaluate the cell cycle and apoptosis of TECs. RESULTS: The analysis revealed that the TOPK activity was significantly suppressed by cisplatin, both in vivo and in vitro. Furthermore, the pharmacological inhibition of TOPK by OTS514, a specific inhibitor of TOPK, exacerbated the cisplatin-induced cell cycle arrest in the G2/M phase and apoptosis of cultured TECs. Moreover, the TOPK activation via the TOPK-T9E plasmid transfection could partially reverse the cell cycle arrest at the G2/M phase and apoptosis of cisplatin-treated TECs. In addition, AKT/protein kinase B (PKB), as a TOPK target protein, was inhibited by cisplatin in cultured TECs. The pharmaceutical inhibition of AKT further aggravated the apoptosis of TECs induced by cisplatin or TOPK inhibition. TOPK systematically mediated the apoptosis via the AKT pathway in the CP-AKI cell model. CONCLUSION: These results indicate that TOPK activation protects against CP-AKI by ameliorating the G2/M cell cycle arrest and cell apoptosis.

mTOR complex-2 activates ENaC by phosphorylating SGK1.

The serum- and glucocorticoid-induced kinase 1 (SGK1) plays a central role in hormone regulation of epithelial sodium (Na+) channel (ENaC)-dependent Na+ transport in the distal nephron. Phosphorylation within a carboxy-terminal domain, designated the hydrophobic motif (HM), determines the activity of SGK1, but the identity of the HM kinase is unknown. Here, we show that the highly conserved serine-threonine kinase mammalian target of rapamycin (mTOR) is essential for the phosphorylation of the HM of SGK1 and the activation of ENaC. We observed that mTOR, in conjunction with rictor (mTORC2), phosphorylated SGK1 and stimulated ENaC. In contrast, when mTOR assembled with raptor in the rapamycin-inhibited complex (mTORC1), it did not phosphorylate SGK1 or stimulate ENaC. Inhibition of mTOR blocked both SGK1 phosphorylation and ENaC-mediated Na+ transport, whereas specific inhibition of mTORC1 had no effect. Similarly, small hairpin RNA-mediated knockdown of rictor inhibited SGK1 phosphorylation and Na+ current, whereas knockdown of raptor had no effect. Finally, in co-immunoprecipitation experiments, SGK1 interacted selectively with rictor but not with raptor, suggesting selective recruitment of SGK1 to mTORC2. We conclude that mTOR, specifically mTORC2, is the HM kinase for SGK1 and is required for ENaC-mediated Na+ transport, thereby extending our understanding of the molecular mechanisms underlying Na+ balance.

Serum and Glucocorticoid-Inducible Kinase 3/Nedd4-2 Signaling Pathway Participates in Podocyte Injury by Regulating the Stability of Nephrin.

Serum and glucocorticoid-inducible kinase 3 (SGK3) is involved in maintaining podocyte function by regulating the protein levels of podocin and CD2-associated protein. Nephrin is also one of the slit diaphragm proteins of podocytes, but whether SGK3 participates in podocyte injury by regulating the levels of nephrin remains unclear. In this study, we focused on whether SGK3 affects nephrin levels and the mechanisms involved in the same. In the kidneys of adriamycin (ADR)-induced podocyte injury mouse model, the protein levels of SGK3 and nephrin were significantly decreased. Furthermore, the expression of SGK3 was negatively correlated with the output of proteinuria, and positively correlated with the levels of nephrin. In ADR-treated conditionally immortalized mouse podocyte cells (MPCs), the protein levels of nephrin and SGK3 were inhibited, while the constitutive expression of SGK3 reversed the ADR-induced decline in nephrin protein levels. Furthermore, ADR treatment or SGK3 inactivation enhanced the ubiquitin-proteasome degradation of nephrin in MPCs, and dramatically activated downstream effector proteins of SGK3, neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2) and glycogen synthase kinase-3 ß (GSK3ß). Similarly, Nedd4-2 or GSK3ß overexpression resulted in increased activity of Nedd4-2 or GSK3ß, and significantly downregulated nephrin levels. Interestingly, ubiquitin-mediated protein degradation of nephrin was regulated by Nedd4-2, rather than by GSK3ß. In summary, SGK3 inactivation downregulated the levels of nephrin by increasing Nedd4-2 and GSK3ß activity in ADR-induced podocyte injury model; in particular, the SGK3/Nedd4-2 signaling pathway was found to be involved in ubiquitin-mediated proteasome degradation of nephrin.

Mechanistic insights into the renoprotective role of curcumin in cisplatin-induced acute kidney injury: network pharmacology analysis and experimental validation.

Cisplatin-induced acute kidney injury (CP-AKI) is a severe complication in patients receiving CP chemotherapy. However, effective therapies for CP-AKI are currently lacking. Curcumin (CUR), a natural polyphenol, is extracted from the rhizome of turmeric and has been reported to have nephroprotective activity. However, the role of CUR in CP-AKI remains unclear. This study aimed to explore the mechanism of CUR in CP-AKI by combining a network pharmacology approach with experimental validations. The analysis revealed 176 potential targets of CUR based on the HERB database and 1,286 related targets of CP-AKI from the GeneCards, DrugBank, and OMIM databases. Further, 106 common targets of CUR against CP-AKI were obtained, and these common targets constructed a protein-protein interaction (PPI) network. In addition, the core targets were screened from the PPI network using Cytoscape. Molecular docking revealed that CUR displayed the best binding to AKT1. Gene Ontology (GO) analysis indicated that the primary biological processes of CUR against CP-AKI included cellular response to chemical stress and apoptotic regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the PI3K-Akt signaling pathway was most significantly enriched in CUR against CP-AKI. Western blotting and flow cytometry showed that CUR inhibited apoptosis induced by CP by activating the Akt signaling pathway in human kidney tubular epithelial cells (HK-2). Altogether, our findings demonstrated that CUR alleviated apoptosis by activating the Akt signaling pathway in CP-AKI in vitro. These data provide a scientific basis for future investigations into the clinical application of CUR against CP-AKI.

[Tapping along meridians on back combined with acupuncture of "Qi Shen Zhen" (Seven acupoints for regulating mind) improves symptoms of post-stroke anxiety disorder patients].

OBJECTIVE: To observe the effect of round magnetic needle tapping along meridians on the back plus acupuncture at "Qi Shen Zhen"（including Shenting ［GV24］, Benshen ［GB13］, Sishenchong ［EX-HN1］）, and Baihui （GV20）, Shenmen （HT7） on gastrointestinal function, daily living activities and anxiety status in post-stroke anxiety disorder (PSAD) patients. METHODS: Fifty-seven PSAD patients were randomly divided into acupuncture group (28 cases) and medication group (29 cases). On the basis of routine treatment and physical therapy, patients of the acupuncture group were treated by applying round magnetic needle to mildly tapping the second line→the first line of the Bladder Meridian→Jiaji acupoints→Governor Meridian on the back from outside to the inside in sequence for 20 min, followed by needling GV24, GV20, GB13, EX-HN1 and HT7, respectively, with the needles retained for 30 min after one minute's twisting. The treatment was conducted once daily, 5 times a week, for 6 weeks. Patients of the medication group were asked to take Escitalopram Oxalate tablets (5-20 mg/d) for 6 weeks. The Hamilton Anxiety Rating Scale (HAMA) was used to assess the patient's severity of anxiety, cognition, somatic sensation, symptoms of cardiovascular, respiratory, gastrointestinal, urogenital, automatic and muscular systems, the Barthel Index (BI) used to evaluated the activities of daily living (ADL), and the gastrointestinal function （Spleen-stomach Symptom Score ［SSS］） assessed according to the "Standards for Diagnosis and Curative Effect Evaluation of Syndromes of Traditional Chinese Medicine". The adverse reactions were observed at the end of treatment. RESULTS: After the treatment, the HAMA scores at the 2nd, 4th and 6th week and the SSS scores at the 4th and 6th week were significantly decreased (P<0.05), and the BI scores at the 2nd， 4th and 6th week were considerably increased in both acupuncture and medication groups compared with their own pre-treatment (P<0.05). The HAMA score at the 2nd week, and the SSS scores at the 2nd, 4th and 6th week were obviously lower(P<0.05), and the BI score at the 6th week was notably higher in the acupuncture group than in the medication group (P<0.05). No significant diffe-rence was found between the two groups in the therapeutic effect of anxiety state (P>0.05). The acupuncture group had fewer adverse reactions than the medication group (P<0.05). CONCLUSION: The round magnetic needle tapping plus "Qi Shen Zhen" needling has a significant therapeutic effect in improving PSAD patients' anxiety state, being similar to Escitalopram Oxalate tablets in reducing anxiety state and being superior to Escitalopram in improving gastrointestinal function and daily living activities.

Pseudothrombus deposition accompanied with minimal change nephrotic syndrome and chronic kidney disease in a patient with Waldenström's macroglobulinemia: A case report.

BACKGROUND: Waldenström's macroglobulinemia (WM) is a rare lymphoid neoplasia, which can have renal complications. These rarely occur, and most common renal manifestations are mild proteinuria and microscopic hematuria. Herein we describe a case of WM that presented with pseudothrombi depositing in capillaries associated with minimal change nephrotic syndrome and chronic kidney disease (CKD). CASE SUMMARY: A 52-year-old man presented with features suggesting nephrotic syndrome. Extensive workups were done, and there were elevated serum levels of interleukin-6 and vascular endothelial growth factor (VEGF), capillary pseudothrombus accumulation associated with minimal change nephrotic syndrome, CKD, and WM. Treatment was directed at the patient's WM with bortezomib, thalidomide, and dexamethasone whereby serum immunoglobulin M (IgM) decreased. The damage of IgM on the kidney was corrected; thus, the patient's proteinuria and serum creatinine had improved. The patient is still under clinical follow-up. CONCLUSION: It is essential for clinicians to promptly pay more attention to patients presenting with features of nephrotic syndrome and do extensive workups to come up with a proper therapy strategy.

The SGK3-triggered ubiquitin-proteasome degradation of podocalyxin (PC) and ezrin in podocytes was associated with the stability of the PC/ezrin complex.

Podocyte damage is commonly accompanied by destabilization of the podocalyxin (PC)/ezrin complex. Serum- and glucocorticoid-inducible kinase 3 (SGK3) plays a role in the maintenance of podocyte function, but the details of this role are poorly understood. Herein we demonstrated that SGK3 and its downstream target protein neural precursor cell expressed developmentally downregulated protein 4 subtype 2 (Nedd4-2) triggered PC and ezrin interaction. In adriamycin (ADR)-induced nephritic mice, and after puromycin aminonucleoside (PAN)-induced podocyte damage in vitro, PC and ezrin protein expression levels decreased significantly, while Nedd4-2 activity increased. Moreover, PAN treatment increased PC and ezrin ubiquitination and decreased PC/ezrin interaction in cultured mouse podocytes. The downregulation of SGK3 activity in mouse podocytes resulted in decreased PC and ezrin protein expression and increased the ubiquitin-proteasome degradation of PC and ezrin. Furthermore, upregulation of SGK3 activity mostly reversed the PAN-induced decrease in PC and ezrin protein expression. Overexpression of Nedd4-2 led to decreased ezrin protein expression via the upregulation of ezrin ubiquitination. In contrast, Nedd4-2 knockdown resulted in increased ezrin protein expression but decreased ezrin ubiquitination. In PC-transfected human embryonic kidney (HEK293T) cells, SGK3 activity downregulation and Nedd4-2 overexpression resulted in decreased PC/ezrin interaction. These results suggested that SGK3 triggers the ubiquitin-proteasome degradation of PC and ezrin, while the SGK3/Nedd4-2 signaling pathway regulates ezrin, but not PC, ubiquitination. Thus SGK3 helps to regulate podocyte function by maintaining the stability of the PC/ezrin complex.

[Protein kinase C-betaI, betaII in mouse diabetic nephropathy kidney and its relation to nephroprotective actions of the angiotensin receptor blocker telmisartan].

OBJECTIVE: To investigate the localization and expression of protein kinase C (PKC)-betaI, betaII in diabetic nephropathy (DN) mouse kidney and its relation to angiotensin receptor blocker telmisartan (Micardis). METHODS: Eighteen mice were divided into three groups: normal group, DN group and Micardis-treated group (n = 6, each group). The expression of PKC-betaI, betaII, transforming growth factor- beta 1 (TGF-beta1) and vascular endothelial growth factor (VEGF) in glomeruli was measured by semiquantitative immunofluorescence histochemistry, the localization of PKC-betaI, betaII was detected by confocal immunofluorescence laser scanning microscopy and the expression of PKC-betaI, betaII in renal cortex, outer and inner medulla were evaluated by semiquantitative Western blotting. RESULTS: Compared to normal mice, the expression of PKC-betaI and betaII on apical membrane of proximal tubule epithelial cells of DN mice was significantly increased, whereas the expression of PKC-betaII on cortical and inner medullary collecting duct was decreased. Western blotting detected increasing expression of PKC-betaI in the renal cortex and outer medulla (P < 0.01), and decreasing expression of PKC-betaII in renal cortex of DN mice (P < 0.01). Enhanced expression of PKC-betaI as well as TGF-beta1 and VEGF (P < 0.01) were shown in the glomeruli of DN mice, where the expression of PKC-betaII was decreased (P < 0.05). Meanwhile, PKC-betaI exhibited a positive correlation to TGF-beta1 (r = 0.649, P = 0.030), but no correlation to VEGF (r = 0.387, P = 0.079). Micardis could partly attenuate above changes. CONCLUSION: The localization and expression of PKC-betaI, betaII are altered in DN mice, PKC-betaI, betaII may change the function of proximal tubule and PKC-betaI may contribute to glomerular hypertrophy through influencing the expression of glomerular TGF-beta1. Treatment with Micardis can partly improve the abnormal expression and distribution of PKC-betaI, betaII in kidneys of DN mice, which suggests that renin-angiotensin-system is implicated in the pathogenesis of DN by regulating the expression and activation of PKC-betaI, betaII isoforms.