Three new glycosides from the stems of Eurya chinensis R. Br.

Two new phenolic glycosides (1 and 2), one known analogue (3), along with a new diterpene glucoside (4) were obtained from ethanolic extract of the stems of Eurya chinensis R. Br. The structures of these isolated compounds were identified by extensive analysis of HRESIMS and NMR spectroscopic data. The cytotoxicities of these compounds were evaluated on MCF-7, A549, HepG2, CaCo2 and 5-8 F cell lines by MTT method, but no obvious activities were observed.

ABO-incompatible living donor kidney transplantation failure due to acute blood group antibody-dependent rejection triggered by human parvovirus B19 infection: a case report and literature review.

Background: With the improvement of immunosuppressive regimens, the success rate and availability of ABO-incompatible (ABO-i) kidney transplantation (KT) have gradually increased. However, the management of immunosuppression protocols and complications associated with ABO-i KT is complex. Here, we report a clinical case of ABO-i living donor KT with allograft dysfunction caused by acute blood group antibody-dependent rejection triggered by human parvovirus B19 (B19V). Case report: The ABO blood group of the recipient was O, and that of the donor was B. The recipient had high baseline anti-B antibody titers (IgM, 1:1024; IgG, 1:64). Before transplantation, he completed a desensitization protocol comprising plasma exchange, double-filtration plasmapheresis, and rituximab, which maintained a low blood group antibody level and resulted in successful transplantation. Two weeks after surgery, the recipient developed a B19V infection combined with acute T-cell-mediated rejection. After the anti-rejection regimen, acute rejection (AR) was successfully reversed, but B19V persisted. One week after AR stabilization, the patient experienced acute antibody-mediated rejection that was more severe and refractory, resulting in the loss of the transplanted kidney. Conclusion: Desensitization combined with immunosuppressants can lead to overimmunosuppression and cause various infections. Infections could break the accommodation state of the patient, thereby inducing AR and resulting in the loss of the transplanted kidney.

Sirolimus in combination with low-dose extended-release tacrolimus in kidney transplant recipients.

Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.

Intravenous immunoglobulin in kidney transplantation: Mechanisms of action, clinical applications, adverse effects, and hyperimmune globulin.

Intravenous immunoglobulin (IVIG) has been developed for over 40 years. The mechanisms of action of IVIG are complex and diverse, and there may be multiple mechanisms that combine to influence it. IVIG has been used in kidney transplantation for desensitization, treatment of antibody-mediated rejection, and ABO-incompatible transplantation. and treatment or prevention of some infectious diseases. Hyperimmune globulins such as cytomegalovirus hyperimmune globulin (CMV-IG) and hepatitis B hyperimmune globulin (HBIG) have also been used to protect against cytomegalovirus and hepatitis B virus, respectively. However, IVIG is also associated with some rare but serious adverse effects and some application risks, and clinicians need to weigh the pros and cons and develop individualized treatment programs to benefit more patients. This review will provide an overview of the multiple mechanisms of action, clinical applications, adverse effects, and prophylactic measures of IVIG, and hyperimmune globulin will also be introduced in it.

HDAC6 inhibition: a significant potential regulator and therapeutic option to translate into clinical practice in renal transplantation.

Histone deacetylase 6 (HDAC6), an almost exclusively cytoplasmic enzyme, plays an essential role in many biological processes and exerts its deacetylation-dependent/independent effects on a variety of target molecules, which has contributed to the flourishing growth of relatively isoform-specific enzyme inhibitors. Renal transplantation (RT) is one of the alternatively preferred treatments and the most cost-effective treatment approaches for the great majority of patients with end-stage renal disease (ESRD). HDAC6 expression and activity have recently been shown to be increased in kidney disease in a number of studies. To date, a substantial amount of validated studies has identified HDAC6 as a pivotal modulator of innate and adaptive immunity, and HDAC6 inhibitors (HDAC6i) are being developed and investigated for use in arrays of immune-related diseases, making HDAC6i a promising therapeutic candidate for the management of a variety of renal diseases. Based on accumulating evidence, HDAC6i markedly open up new avenues for therapeutic intervention to protect against oxidative stress-induced damage, tip the balance in favor of the generation of tolerance-related immune cells, and attenuate fibrosis by inhibiting multiple activations of cell profibrotic signaling pathways. Taken together, we have a point of view that targeting HDAC6 may be a novel approach for the therapeutic strategy of RT-related complications, including consequences of ischemia-reperfusion injury, induction of immune tolerance in transplantation, equilibrium of rejection, and improvement of chronic renal graft interstitial fibrosis after transplantation in patients. Herein, we will elaborate on the unique function of HDAC6, which focuses on therapeutical mechanism of action related to immunological events with a general account of the tantalizing potential to the clinic.

Four new stilbenes and one new flavonoid with potential antibacterial and anti-SARS-CoV-2 activity from Cajanus cajan.

Four new stilbenes (1-4) and one new flavonoid (5), named cajanines D-H, together with three known stilbenes (6-8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1-4 bore an isopentyl side chain, and further hydroxylation of compounds 1-3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1-8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC50 values of compounds 5-7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity.

Study on the Relationship Between Differentially Expressed Proteins in Breast Cancer and Lymph Node Metastasis.

INTRODUCTION: Lymph node metastasis is a cause of poor prognosis in breast cancer. Mass spectrometry-based proteomics aims to map the protein landscapes of biological samples and profile tumors more comprehensively. Here, proteomics was employed to identify differentially expressed proteins (DEPs) that were associated with lymph node metastasis. METHODS: Tandem mass tag (TMT) quantitative proteomic approaches were applied for extensive profiling of conditioned medium of MDA-MB-231 and MCF7 cell lines and serums of patients who did or did not have lymph node metastasis, and DEPs were analyzed by bioinformatics. Furthermore, potential secreted or membrane proteins MUC5AC, ITGB4, CTGF, EphA2, S100A4, PRDX2, and PRDX6 were selected for verification in 114 tissue microarray samples of breast cancer using the immunohistochemical method. The relevant data was analyzed and processed by independent sample t test, chi-square test, or Fisher's exact test using SPSS 22.0 software. RESULTS: In the conditioned medium of MDA-MB-231 cell lines, 154 proteins were upregulated, while 136 were downregulated compared to those of MCF7. In the serum of patients with breast cancer and lymph node metastasis, 17 proteins were upregulated, and 5 proteins were downregulated compared to those without lymph node metastasis. Furthermore, according to tissue verification, CTGF, EphA2, S100A4, and PRDX2 were associated with breast cancer lymph node metastasis. CONCLUSION: Our study provides a new perspective for the understanding of the role of DEPs (especially CTGF, EphA2, S100A4, and PRDX2) in the development and metastasis of breast cancer. They could become potential diagnostic and prognostic biomarkers and therapeutic targets.

Three stilbenes from pigeon pea with promising anti-methicillin-resistant Staphylococcus aureus biofilm formation activity.

Cajaninstilbene acid (CSA), longistylin A (LLA), and longistylin C (LLC) are three characteristic stilbenes isolated from pigeon pea. The objective of this study was to evaluate the antibacterial activity of these stilbenes against Staphylococcus aureus and even methicillin-resistant Staphylococcus aureus (MRSA) and test the possibility of inhibiting biofilm formation. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these stilbenes were evaluated. And the results showed that LLA was most effective against tested strains with MIC and MBC values of 1.56 µg/mL followed by LLC with MIC and MBC values of 3.12 µg/mL and 6.25 µg/mL as well as CSA with MIC and MBC values of 6.25 µg/mL and 6.25-12.5 µg/mL. Through growth curve and cytotoxicity analysis, the concentrations of these stilbenes were determined to be set at their respective 1/4 MIC in the follow-up research. In an anti-biofilm formation assay, these stilbenes were found to be effectively inhibited bacterial proliferation, biofilm formation, and key gene expressions related to the adhesion and virulence of MRSA. It is the first time that the anti-S. aureus and MRSA activities of the three stilbenes have been systematically reported. Conclusively, these findings provide insight into the anti-MRSA mechanism of stilbenes from pigeon pea, indicating these compounds may be used as antimicrobial agents or additives for food with health functions, and contribute to the development as well as application of pigeon pea in food science.

The sesquiterpenes with the COVID-19 Mpro inhibitory activity from the Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded four new sesquiterpenes including a novel skeleton (claroguaiane A, 1), two guaianolides (claroguaianes B-C, 2-3), and one eudesmanolide (claroeudesmane A, 4), together with three known sesquiterpenoids (5-7). The structures of the new compounds were elucidated by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitive activity of COVID-19 Mpro. As a result, compound 5 showed moderate activity with an IC50 value of 36.81 µM and compound 6 exhibited a potent inhibitory effect with an IC50 value of 16.58 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic.

BACKGROUND: Functional constipation (FC) in children affects their growth, development and quality of life. L-pipecolic acid (L-PA) was decreased in FC children based on gut microbiome and serum metabolomic. In this study, loperamide-induced constipation in mice was used to evaluate the effects of L-PA on constipated mice. METHOD: 26 FC and 28 healthy children were recruited. Stool samples and serum samples were subjected to 16S rDNA sequencing and ultra-performance liquid chromatography/quadrupole time of flight (UPLC-Q/TOF-MS) approach, respectively. A loperamide-induced mouse constipation model was developed, and all mice were randomly divided into control (Con), loperamide (Lop) and L-PA (Lop + L-PA) treatment groups (6 mice per group). The mice in the Lop + L-PA group were given L-PA (250 mg/kg, once a day) and loperamide; the Lop group was given loperamide for 1 week, and the Con group was given saline. The fecal parameters and intestinal motility of mice in each group were detected. serum 5-HT levels and colon 5-HT expression were detected by ELISA and immunohistochemistry, respectively; qRT-PCR was used to detect the expression of AQP3 and 5-HT4R mRNA in each group. RESULTS: 45 differential metabolites and 18 significantly different microbiota were found in FC children. The α and ß diversity of gut microbiota in FC children was significantly reduced. Importantly, serum L-PA was significantly reduced in FC children. The KEGG pathway enrichment were mainly enriched in fatty acid biosynthesis, lysine degradation, and choline metabolism. L-PA was negatively associated with Ochrobactrum, and N6, N6, N6-trimethyl-l-lysine was positively associated with Phascolarcrobacterium. In addition, L-PA improved the fecal water content, intestinal transit rate, and increased the serum 5-HT levels in constipated mice. Moreover, L-PA increased the expression of 5-HT4R, reduced AQP3, and regulated constipation-associated genes. CONCLUSIONS: Gut microbiota and serum metabolites were significantly altered in children with FC. The abundance of Phascolarctobacterium and Ochrobactrum and serum L-PA content were decreased in FC children. L-PA was found to alleviate the fecal water content, increase intestinal transit rate and the first black stool defecation time. L-PA improved constipation by increasing 5-HT and 5-HT4R expression while down-regulating AQP3 expression.

Fluorescent Probes with Variable Intramolecular Charge Transfer: Constructing Closed-Circle Plots for Distinguishing D2O from H2O.

It is difficult to distinguish between H2O and D2O due to their very similar properties. Triphenylimidazole derivatives with carboxyl groups (TPI-COOH-2R) show intramolecular charge transfer that responds to polarities and pH of solvents. Here, a series of TPI-COOH-2R with very high photoluminescence quantum yields (73-98%) were synthesized to distinguish D2O from H2O by the method of wavelength-changeable fluorescence. In a mixed THF/water solution, the increase of H2O and D2O contents will separately induce different pendulum-type fluorescence variations and form plots of closed circles with the same starting and ending points from which a THF/water ratio that displays the most different emission wavelengths (up to 53 nm with an LOD of 0.064 vol %) can be determined to further distinguish D2O from H2O. This is proved to be originated from the various Lewis acidities between H2O and D2O. The results of theoretical calculations and experiments suggest that, for different substituent groups in TPI-COOH-2R, an appropriate electron-donating effect is beneficial to distinguish between H2O and D2O, while the electron-pulling effect is adverse. Moreover, because the potential hydrogen/deuterium exchange does not affect the as-responsive fluorescence, this method is reliable. And this work provides a new strategy for the design of fluorescent probes for D2O.

Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

A Lesson of Immunosuppression in Renal Transplant: Retreat or Hold?

Background: Aiming at understanding whether there are cases of near-tolerance among long-term surviving kidney transplant recipients in our center, or even operant tolerance can be attempted based on their immune status, we analyzed changes of immune cell subsets and cytokines in various groups, and evaluated immune status of long-term survival recipients. Methods: A real-world, observational, retrospective cohort study was conducted in our hospital. Twenty-eight long-term recipients were selected as study subjects, 15 recent postoperative stable recipients, and 15 healthy subjects as controls. T and B lymphocyte subsets, MDSCs, and cytokines were detected and analyzed. Results: Treg/CD4 T cells, total B and B10 cells in long-term and recent renal recipients were lower than healthy controls (HC). The level of IFN-γ and IL-17A in long-term survival patients was obviously higher than that in recent postoperative stable recipients and HC, while TGF-ß1 level was significantly lower in long-term survival group than in short-term postoperative group and HC. Notably, compared with short-term recipients, it has been found that the IL-6 level in both positive and negative HLA groups were obviously lower (all P<0.05). In the long-term survival group, 43% of recipients were positive for urinary protein and 50% were positive for HLA antibody. Conclusion: This "real-world" study validates the findings of real status of long-term survival recipients observed in clinical trials. Contrary to a state of proper tolerance as expected, the group recipients in long-term survival were accompanied by the increased indicators of immune response, while those related to immune tolerance were not significantly increased. Long-term survival recipients with stable renal function may be in an immune equilibrium state where immunosuppression and rejection coexist under the action of low-intensity immune agents. If immunosuppressive agents are reduced or even removed, rejection may occur.

Gene signature and prediction model of the mitophagy-associated immune microenvironment in renal ischemia-reperfusion injury.

Background: Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes. Method: The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson's correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections. Results: The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable. Conclusion: We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.

Clinical efficacy and complications of transurethral resection of the prostate versus plasmakinetic enucleation of the prostate.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly males, and many kinds of minimally invasive procedures can be used for the treatment of BPH. However, various procedures have caused some controversies regarding clinical outcomes, so more studies are needed to validate these controversial topics. AIMS: This study aimed to explore differences of clinical efficacy, surgical features, and complications between transurethral resection of the prostate (TURP) and plasmakinetic enucleation of the prostate (PKEP) for BPH. METHODS: A total of eligible 850 cases of BPH underwent TURP (the TURP group, 320 cases) or PKEP (the PKEP group, 530 cases) in the urology department of our hospital from March 2015 to 2018 were involved in this study. Then, the baseline data, surgical characteristics, IPSS, QoL, PVR, Qmax, IIEF-5, and documented complications were compared between the two groups. RESULTS: The operative time, intraoperative irrigation volume, postoperative hemoglobin, decrease in hemoglobin, postoperative irrigation time and volume, catheterization time, and hospital stay of the PKEP group were significantly less than those of the TURP group (all P < 0.05). At 3 months, 1, 2, and 3 years after operation, no significant differences were observed in IPSS, QoL, PVR, but the results of Qmax and IIEF-5 in the PKEP group were significantly higher than those parameters in the TURP group (all P < 0.05). The incidences of massive blood loss, postoperative secondary bleeding, blood transfusion, capsular perforation, urinary tract irritation, bladder spasm, clot retention, urinary tract infection, transient incontinence, erectile dysfunction, and the incidences of II, III grade of Clavien-Dindo classification in the PKEP group were significantly lower than those of the TURP group (all P < 0.05). CONCLUSION: The clinical efficacy of PKEP is compared favorably with TURP during midterm follow-up. Given the merits such as less blood loss and hospital stay, lower complications, PKEP should be given a priority for BPH.

Euryachincoside, a Novel Phenolic Glycoside with Anti-Hepatic Fibrosis Activity from Eurya chinensis.

Eurya chinensis has been recorded as a folk medicine traditionally used for treatment of a variety of symptoms. However, the phytochemical and pharmacological investigations of this plant are still scarce. A novel phenolic glycoside named Euryachincoside (ECS) was isolated by chromatographic separation from E. chinensis, and its chemical structure was identified by analysis of HRMS and NMR data. Its anti-hepatic fibrosis effects were evaluated in both HSC-T6 (rat hepatic stellate cells) and carbon tetrachloride (CCl4)-induced mice with Silybin (SLB) as the positive control. In an in vitro study, ECS showed little cytotoxicity and inhibited transforming growth factor-beta (TGF-ß)-induced Collagen I (Col1) along with alpha-smooth muscle actin (α-SMA) expressions in HSC-T6. An in vivo study suggested ECS significantly ameliorated hepatic injury, secretions of inflammatory cytokines, and collagen depositions. Moreover, ECS markedly mediated Smad2/3, nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways both in vitro and vivo. These present findings confirmed that ECS is a novel phenolic glycoside from E. chinensis with promising curative effects on hepatic fibrosis, and its mechanisms may include decreasing extracellular matrix accumulation, reducing inflammation and attenuating free radicals via Smad2/3, NF-κB and Nrf2 signaling pathways, which may shed light on the exploration of more effective phenolic glycoside-based anti-fibrotic agents.

Two new withanolides from the whole plants of Physalis peruviana.

Two new withaphysalin-type withanolides (18-O-ethylwithaphysalin R and 5-O-ethylphysaminimin C, 1 and 2), along with twelve known withanolides (3-14), were purified and identified from Physalis peruviana L. The chemical structures of these new isolates were elucidated through analyzing spectroscopic and HRESIMS data. All the obtained metabolites were appraised for their potential antiproliferative activity against the human breast cancer cell line MCF-7. Compound 7 was discovered to exhibit potent activity with an IC50 value of 3.51 µM and compounds 2, 6 and 14 showed weak cytotoxic effect.

Nitrate Quantification in Fresh Vegetables in Shanghai: Its Dietary Risks and Preventive Measures.

To investigate nitrate and nitrite content in fresh vegetables, 264 samples were randomly collected in the farmers' markets in Shanghai, Southeast China. The results indicate that 25.0% of the fresh vegetables were critically or more contaminated by nitrate [>1440 mg/kg FW (Fresh weight)]. Generally, leafy vegetables were more highly enriched in nitrate than root-tuber and fruit vegetables. About 22.6% of the leafy vegetables had a nitrate content exceeding the limit for edible permission (>3000 mg/kg FW). Nitrite content in the fresh vegetables was all within the safe level (<1 mg/kg FW). It was estimated that the daily nitrate intake through eating vegetables in Shanghai exceeded the WHO/FAO allowable limit. The field experiment indicated that the hyper-accumulation of nitrate and nitrite in the vegetables was mainly attributed to the excessive application of chemical fertilizers. The maxima of nitrate and nitrite in the vegetables were attained one week after applying chemical fertilizer, and thus they cannot be picked for dietary use. Applying organic manure can effectively lower the risk of nitrate and nitrite contamination in vegetables. The old leaves and leaf petioles were more easily enriched in nitrate due to their weaker metabolic activity. Vegetables with high nitrate content had a high risk of nitrite toxicity during storage due to the biological conversion of nitrate into nitrite, which is easily triggered by suitable temperature and mechanical damage processing. Therefore, fresh vegetables should be stored by rapid cooling and in undamaged forms to prevent nitrite accumulation.

Analysis of ARHGAP4 Expression With Colorectal Cancer Clinical Characteristics and Prognosis.

Background: This study aims to analyze the correlation between ARHGAP4 in the expression and clinical characteristics of colorectal cancer (CRC), and the influence of ARHGAP4 expression on the prognosis of CRC, and to evaluate whether ARHGAP4 is a potential prognostic oncotarget for CRC. Methods: ARHGAP4 was identified using the Gene Expression Omnibus database through weighted gene coexpression network analysis. Using the Gene Expression Profiling Interactive Analysis to perform and analyze the expression and prognosis of ARHGAP4 in CRC. The expression of AGRGAP4 and immune cells was analyzed by the Tumor IMmune Estimation Resource online database. Finally, immunohistochemistry was used to analyze the expression difference and prognosis of ARHGAP4 in CRC and adjacent normal tissues, as well as the relationship between AGRGAP4 expression and clinical features of CRC. Results: We identified ARHGAP4 that is related to the recurrence of CRC from GSE97781 data. ARHGAP4 has not been reported in CRC. The high expression of ARHGAP4 in select colon adenocarcinoma indicates a poor prognosis by database analysis. In our clinical data results, ARHGAP4 is highly expressed in CRC and lowly expressed in normal tissues adjacent to cancer. Compared with the low-expression group, the high-expression group has a significantly poorer prognosis. In colon cancer, the B-cell, macrophage, neutrophil, and dendritic-cell levels are downregulated after ARHGAP4 gene knockout; the levels of CD8+ and CD4+ T cells, neutrophils, and dendritic cells are upregulated after the amplification of the ARHGAP4 gene. In addition, ARHGAP4 expression is related to N,M staging and clinical staging. Conclusion: ARHGAP4 is highly expressed in CRC, and the high expression of ARHGAP4 has a poor prognosis. The expression of ARHGAP4 in CRC is related to the immune cells such as B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells. ARHGAP4 is correlated with N,M staging and clinical staging in CRC. ARHGAP4 may be a potential biomarker for the prognosis of CRC.