Yersinia ruckeri Infection and Enteric Redmouth Disease among Endangered Chinese Sturgeons, China, 2022.

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.

Effects of phoxim on antibacterial infection of silver carp.

The efficacy of phoxim in treating bacterial sepsis in silver carp is significant, yet its underlying mechanism remains elusive. This study aimed to establish a model of Aeromonas veronii infection in silver carp and subsequently treat the infected fish with 10 µg/L phoxim. Kidney and intestine samples from silver carp were collected for transcriptome analysis and assessment of intestinal microbial composition, with the aim of elucidating the mechanism underlying the efficacy of phoxim in treating bacterial sepsis in silver carp. The results of transcriptome and intestinal microbial composition analysis of silver carp kidney indicated that A. veronii infection could up-regulate the expression of il1ß, il6, nos2, ctsl, casp3 et al., which means, signifying that the kidney of silver carp would undergo inflammation, induce apoptosis, and alter the composition of intestinal microorganisms. Phoxim immersion might enhance the energy metabolism of silver carp and change its intestinal microbial composition, potentially elevating the antibacterial infection resistance of silver carp. These findings may contribute to an understanding of how phoxim can effectively treat bacterial sepsis in silver carp.

A Broadband Photodetector Based on Non-Layered MnS/WSe2 Type-I Heterojunctions with Ultrahigh Photoresponsivity and Fast Photoresponse.

The separation of photogenerated electron-hole pairs is crucial for the construction of high-performance and wide-band responsive photodetectors. The type-I heterojunction as a photodetector is seldomly studied due to its limited separation of the carriers and narrow optical response. In this work, we demonstrated that the high performance of type-I heterojunction as a broadband photodetector can be obtained by rational design of the band alignment and proper modulation from external electric field. The heterojunction device is fabricated by vertical stacking of non-layered MnS and WSe2 flakes. Its type-I band structure is confirmed by the first-principles calculations. The MnS/WSe2 heterojunction presents a wide optical detecting range spanning from 365 nm to 1550 nm. It exhibits the characteristics of bidirectional transportation, a current on/off ratio over 103, and an excellent photoresponsivity of 108 A W-1 in the visible range. Furthermore, the response time of the device is 19 ms (rise time) and 10 ms (fall time), which is much faster than that of its constituents MnS and WSe2. The facilitation of carrier accumulation caused by the interfacial band bending is thought to be critical to the photoresponse performance of the heterojunction. In addition, the device can operate in self-powered mode, indicating a photovoltaic effect.

Integrating Low-Stack Photonic Crystals with the Honeycomb-like Structural Framework to Enhance the Photovoltaic Performance in Perovskite Solar Cells.

An inverse opal structure of SnO2 with a honeycomb morphology is introduced as the framework for the attached perovskite materials and functional layers in the hybrid perovskite-based solar cells simultaneously. Three different pore sizes of polystyrene microsphere layers, with diameters of 350, 480, and 600 nm, were fabricated through a vertical self-assembly vaporization technique. The polystyrene (PS) layer served as the sacrificial template for the inverse opal structure. By controlling the spinning parameters, the inverse opal-structured SnO2 layer was used to constrain them into a single-layer stacking structure. These layers with varying pore sizes were subsequently applied onto a dense electron transport layer that is in contact with the perovskite layer. A carbon electrode is used as photovoltaic solar cells. The major benefits of this approach were systematically analyzed through structural characterizations and various means. The semiphotonic crystal layer induces modulation effects, resulting in increased light absorption and surface area, which leads to a substantial increase in short-circuit density. By studying the electrochemical properties in the dark to exclude the influence of optical effects, we attribute the slight increase in the fill factor to the increased surface area, which enhances carrier transport. Among the different layers, the inverse opal layer prepared with 480 nm polystyrene microspheres displayed superior photovoltaic performance parameters due to its appropriate surface area and relatively higher light absorption. The power conversion efficiency of the MAPbI3 perovskite solar cell showed a relative enhancement of 55%. Additionally, aging tests demonstrated that devices with the additional structural layer exhibited good endurance under conventional atmospheric conditions after 1440 h of aging.

Mechanism of sturgeon intestinal inflammation induced by Yersinia ruckeri and the effect of florfenicol intervention.

The mechanism by which Y. ruckeri infection induces enteritis in Chinese sturgeon remains unclear, and the efficacy of drug prevention and control measures is not only poor but also plagued with numerous issues. We conducted transcriptomic and 16 S rRNA sequencing analyses to examine the differences in the intestinal tract of hybrid sturgeon before and after Y. ruckeri infection and florfenicol intervention. Our findings revealed that Y. ruckeri induced the expression of multiple inflammatory factors, including il1ß, il6, and various chemokines, as well as casp3, casp8, and multiple tumor necrosis factor family members, resulting in pathological injury to the body. Additionally, at the phylum level, the relative abundance of Firmicutes and Bacteroidota increased, while the abundance of Plesiomonas and Cetobacterium decreased at the genus level, altering the composition of the intestinal flora. Following florfenicol intervention, the expression of multiple apoptosis and inflammation-related genes was down-regulated, promoting tissue repair. However, the flora became further dysregulated, increasing the risk of infection. In conclusion, our analysis of the transcriptome and intestinal microbial composition demonstrated that Y. ruckeri induces intestinal pathological damage by triggering apoptosis and altering the composition of the intestinal microbiota. Florfenicol intervention can repair pathological damage, but it also exacerbates flora imbalance, leading to a higher risk of infection. These findings help elucidate the molecular mechanism of Y. ruckeri-induced enteritis in sturgeon and evaluate the therapeutic effect of drugs on intestinal inflammation in sturgeon.

Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer.

Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as "viral mimicry," has emerged as an effective strategy to convert immunologically "cold" tumors into "hot." Through a curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) as a potent repressor of double-stranded RNA (dsRNA) in small cell lung cancers (SCLC). Depletion of DHX9 induced accumulation of cytoplasmic dsRNA and triggered tumor-intrinsic innate immunity. Intriguingly, ablating DHX9 also induced aberrant accumulation of R-loops, which resulted in an increase of DNA damage-derived cytoplasmic DNA and replication stress in SCLCs. In vivo, DHX9 deletion promoted a decrease in tumor growth while inducing a more immunogenic tumor microenvironment, invigorating responsiveness to immune-checkpoint blockade. These findings suggest that DHX9 is a crucial repressor of tumor-intrinsic innate immunity and replication stress, representing a promising target for SCLC and other "cold" tumors in which genomic instability contributes to pathology. SIGNIFICANCE: One promising strategy to trigger an immune response within tumors and enhance immunotherapy efficacy is by inducing endogenous "virus-mimetic" nucleic acid accumulation. Here, we identify DHX9 as a viral-mimicry-inducing factor involved in the suppression of double-stranded RNAs and R-loops and propose DHX9 as a novel target to enhance antitumor immunity. See related commentary by Chiappinelli, p. 389. This article is featured in Selected Articles from This Issue, p. 384.

Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma.

ABSTRACT: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis and limited treatment options. Programmed cell death ligand 1(PD-L1) is recognized to be involved in the pathobiology of ATLL. However, what molecules control PD-L1 expression and whether genetic or pharmacological intervention might modify PD-L1 expression in ATLL cells are still unknown. To comprehend the regulatory mechanisms of PD-L1 expression in ATLL cells, we performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening in this work. In ATLL cells, we discovered that the neddylation-associated genes NEDD8, NAE1, UBA3, and CUL3 negatively regulated PD-L1 expression, whereas STAT3 positively did so. We verified, in line with the genetic results, that treatment with the JAK1/2 inhibitor ruxolitinib or the neddylation pathway inhibitor pevonedistat resulted in a decrease in PD-L1 expression in ATLL cells or an increase in it, respectively. It is significant that these results held true regardless of whether ATLL cells had the PD-L1 3' structural variant, a known genetic anomaly that promotes PD-L1 overexpression in certain patients with primary ATLL. Pevonedistat alone showed cytotoxicity for ATLL cells, but compared with each single modality, pevonedistat improved the cytotoxic effects of the anti-PD-L1 monoclonal antibody avelumab and chimeric antigen receptor (CAR) T cells targeting PD-L1 in vitro. As a result, our work provided insight into a portion of the complex regulatory mechanisms governing PD-L1 expression in ATLL cells and demonstrated the in vitro preliminary preclinical efficacy of PD-L1-directed immunotherapies by using pevonedistat to upregulate PD-L1 in ATLL cells.

The RNA-binding motif protein 14 regulates telomere integrity at the interface of TERRA and telomeric R-loops.

Telomeric repeat-containing RNA (TERRA) and its formation of RNA:DNA hybrids (or TERRA R-loops), influence telomere maintenance, particularly in human cancer cells that use homologous recombination-mediated alternative lengthening of telomeres. Here, we report that the RNA-binding motif protein 14 (RBM14) is associated with telomeres in human cancer cells. RBM14 negatively regulates TERRA expression. It also binds to TERRA and inhibits it from forming TERRA R-loops at telomeres. RBM14 depletion has several effects, including elevated TERRA levels, telomeric R-loops, telomere dysfunction-induced DNA damage foci formation, particularly in the presence of DNA replication stress, pRPA32 accumulation at telomeres and telomere signal-free ends. Thus, RBM14 protects telomere integrity via modulating TERRA levels and its R-loop formation at telomeres.

Comparative analysis of the transcriptional responses of Acetilactobacillus jinshanensis BJ01 to organic acids.

As the important functional microorganism in the brewing process of Chinese Baijiu, lactic acid bacteria influences the microbial community and production of flavor substances in the Baijiu brewing process. In this study, we first isolated an Acetilactobacillus jinshanensis strain from baijiu fermented grains and named it A. jinshanensis BJ01. Its optimal growth conditions are 30 °C and pH 3.5. In particular, A. jinshanensis BJ01 cannot utilize inorganic acids and most organic acids, except for lactic acid (HL) and acetic acid (HAc). The observed phenotypes showed good growth with HL. When the mixed acid of HL-HAc (V:V = 1:1) was used, the growth rate of A. jinshanensis BJ01 greatly accelerated. Transcriptomic sequencing revealed the specific responses of the strain to the acidulants used. The number of upregulated genes in HL-HAc medium was more than that in single acid medium (HL or HAc). KEGG enrichment analyses indicated that the glycometabolism level of HAc regulation was relatively downregulated. The gene expression of quorum sensing and ABC transporter pathways were remarkably upregulated under HL-HAc regulation. Pyruvate metabolic pathway may be an important reason for the difference in A. jinshanensis BJ01 response to different organic acids. Our study reported a new organic acid-inducible growth type of bacteria mainly depending on the presence of HL and HAc, and was beneficial to the improvement of fermentation technology of Baijiu.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

Boosting the inherent activity of NiFe layered double hydroxide via erbium incorporation for water oxidation.

Enhancing the inherent activity of transition metal-based compounds involving Ni and Fe for the electrocatalytic oxygen evolution reaction (OER) is of vital importance, especially NiFe layered double hydroxide (LDH). Here, we doped erbium (Er) into NiFe LDH (Er-NiFe LDH) nanostructures using simple liquid-phase synthesis. The OER activity tests at the same mass loading demonstrated that Er-NiFe LDH has a smaller overpotential and lower Tafel slope than undoped NiFe LDH and commercial RuO2 powders, needing only a small overpotential of 243 mV to achieve a constant current at 10 mA cm-2. Additionally, Er-NiFe LDH was grown in situ on hydrophilic carbon paper substrates (Er-NiFe LDH@CP) to fabricate a three-dimensional (3D) electrode with large catalyst loading, which is favorable for analyzing the stability of morphology structure and elementary components after OER measurement. The galvanostatic measurement suggested that the Er-NiFe LDH@CP electrode possess higher electrochemical durability than a modified glassy carbon electrode due to the stronger mechanical binding between Er-NiFe LDH nanostructures and carbon paper substrate. More importantly, physical characterizations (e.g., SEM and XPS) revealed that Er-NiFe LDH has an excellent stability of morphology, and Ni, Fe, and Er still exist on the catalyst 24 h after the operation. This work provides an effective way for improving the inherent catalytic activity and stability of polymetallic OER catalysts in the future.

Effect of Agaricus bisporus Polysaccharides (ABPs) on anti-CCV immune response of channel catfish.

Herein, the effects of Agaricus bisporus Polysaccharides (ABPs) on anti-channel catfish virus (CCV) infections to promote their application in channel catfish culture were explored. Transcriptome and metabolome analyses were conducted on the spleen of a CCV-infected channel catfish model fed with or without ABPs. CCV infections upregulated many immune and apoptosis-related genes, such as IL-6, IFN-α3, IFN-γ1, IL-26, Casp3, Casp8, and IL-10, and activated specific immunity mediated by B cells. However, after adding ABPs, the expression of inflammation-related genes decreased in CCV-infected channel catfish, and the inflammatory inhibitors NLRC3 were upregulated. Meanwhile, the expression of apoptosis-related genes was reduced, indicating that ABPs can more rapidly and strongly enhance the immunity of channel catfish to resist viral infection. Moreover, the metabonomic analysis showed that channel catfish had a high energy requirement during CCV infection, and ABPs could enhance the immune function of channel catfish. In conclusion, ABPs can enhance the antiviral ability of channel catfish by enhancing immune response and regulating inflammation. Thus, these findings provided new insights into the antiviral response effects of ABPs, which might support their application in aquaculture.

Enhanced Reactive Brilliant Blue Removal Using Chitosan-Biochar Hydrogel Beads.

To address the challenges associated with the weak affinity and difficult separation of biochar, we developed chitosan-biochar hydrogel beads (CBHBs) as an efficient solution for removing reactive brilliant blue (RBB KN-R) from wastewater. The adsorption behavior and mechanism of RBB KN-R onto CBHBs were extensively studied. Notably, the adsorption capacity of RBB KN-R showed pH-dependence, and the highest adsorption capacity was observed at pH 2. The adsorption process was well fitted with the pseudo-second-order kinetic model and the intraparticle diffusion model. Film diffusion and intraparticle diffusion were both responsible for the adsorption of RBB KN-R onto CBHBs. At 298.15 K, the maximum adsorption capacity qm was determined to be 140.74 mg/g, with higher temperatures favoring the adsorption process. A complex mechanism involving π-π interactions, electrostatic attraction, hydrophobic interaction, and hydrogen bonding was found to contribute to the overall adsorption process. The experimental data discovered the coexisting substances and elevated ionic strength hindered the adsorption capacity. Significantly, after three cycles of adsorption-desorption, the CBHBs maintained an adsorption capacity above 95% for RBB KN-R. These promising results imply that CBHBs are a durable and cost-effective adsorbent for efficient removal of dyes from wastewater.

Molecular Characterization and Expression Analysis of IL-10 and IL-6 in Channel Catfish (Ictalurus punctatus).

IL-10 and IL-6 play important roles in protecting against inflammation and clearing pathogens from the body. In this study, homologous compounds of IL-10 and IL-6 were identified in channel catfish, and their immune responses were analyzed. The CDS sequences of IL-10 and IL-6 were 549 bp and 642 bp, respectively, and showed the highest homology with Ameiurus melas. In addition, the expression of the IL-10 and IL-6 genes was ubiquitous in 10 tissues examined. IL-10 is highly expressed in the liver and slightly expressed in the gill. The high expression of the IL-6 gene was observed in the spleen, heart, and gonad, with the lowest levels in the liver. LPS, Poly(I:C), PHA, and PMA showed a highly significant increase in IL-10 and IL-6 expression 48 h after CCK stimulation (p < 0.01). Otherwise, Yersinia ruckeri, Streptococcus iniae, channel catfish virus, and deltamethrin induced IL-10 and IL-6 expression, varying in intensity between different organs. Our results suggest that IL-10 and IL-6 are involved in the immune response of the host against the pathogen.

Effects of diets rich in Agaricus bisporus polysaccharides on the growth, antioxidant, immunity, and resistance to Yersinia ruckeri in channel catfish.

To promote the application of Agaricus bisporus polysaccharides (ABPs) in channel catfish (Ictalurus punctatus) culture, we evaluated the effects of ABPs on the growth, immunity, antioxidant, and antibacterial activity of channel catfish. When the amount of ABPs was 250 mg/kg, channel catfish's weight gain and specific growth rates increased significantly while the feed coefficient decreased. We also found that adding ABPs in the feed effectively increased the activities of ACP, MDA, T-SOD, AKP, T-AOC, GSH, and CAT enzymes and immune-related genes such as IL-1ß, Hsp70, and IgM in the head kidney of channel catfish. Besides, long-term addition will not cause pathological damage to the head kidney. When the amount of ABPs was over 125 mg/kg, the protection rate of channel catfish was more than 60%. According to the intestinal transcriptome analysis, the addition of ABPs promoted the expression of intestinal immunity genes and growth metabolism-related genes and enriched multiple related KEEG pathways. When challenged by Yersinia ruckeri infection, the immune response of channel catfish fed with ABPs was intenser and quicker. Additionally, the 16S rRNA gene sequencing analysis showed that the composition of the intestinal microbial community of channel catfish treated with ABPs significantly changed, and the abundance of microorganisms beneficial to channel catfish growth, such as Firmicutes and Bacteroidota increased. In conclusion, feeding channel catfish with ABPs promoted growth, enhanced immunity and antioxidant, and improved resistance to bacterial infections. Our current results might promote the use of ABPs in channel catfish and even other aquacultured fish species.

Analysis and therapeutic targeting of the IL-1R pathway in anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL), a subgroup of mature T-cell neoplasms with an aggressive clinical course, is characterized by elevated expression of CD30 and anaplastic cytology. To achieve a comprehensive understanding of the molecular characteristics of ALCL pathology and to identify therapeutic vulnerabilities, we applied genome-wide CRISPR library screenings to both anaplastic lymphoma kinase positive (ALK+) and primary cutaneous (pC) ALK- ALCLs and identified an unexpected role of the interleukin-1R (IL-1R) inflammatory pathway in supporting the viability of pC ALK- ALCL. Importantly, this pathway is activated by IL-1α in an autocrine manner, which is essential for the induction and maintenance of protumorigenic inflammatory responses in pC-ALCL cell lines and primary cases. Hyperactivation of the IL-1R pathway is promoted by the A20 loss-of-function mutation in the pC-ALCL lines we analyze and is regulated by the nonproteolytic protein ubiquitination network. Furthermore, the IL-1R pathway promotes JAK-STAT3 signaling activation in ALCLs lacking STAT3 gain-of-function mutation or ALK translocation and enhances the sensitivity of JAK inhibitors in these tumors in vitro and in vivo. Finally, the JAK2/IRAK1 dual inhibitor, pacritinib, exhibited strong activities against pC ALK- ALCL, where the IL-1R pathway is hyperactivated in the cell line and xenograft mouse model. Thus, our studies revealed critical insights into the essential roles of the IL-1R pathway in pC-ALCL and provided opportunities for developing novel therapeutic strategies.

The effects of grating anatase on the photovoltaic performance of perovskite based solar cells.

Stimulated by the extraordinary power conversion efficiency (PCE) of hybrid organic-inorganic perovskites (HOIP) based solar cells (SCs), the derivative studies on inorganic perovskites (IOP) based SCs have been intensely investigated. In order to overcome the disadvantages of CsPbBr3, most prominently the unfavorable larger band gap (2.3eV), a grating layer of mesoporous anatase TiO2(mp-TiO2) has been inserted into the conventional configuration of SCs. The grating layer acts as the electron transfer layer (ETL) and light absorption strengthening layer at the same time. Due to the combined effects, the increased contacting area increased the fill factor (FF) and enhanced light trapping in the grating layer increased the short-current density, the average PCE of IOP based SCs has increased from 5.67% to 7.58%, which is a ca. 34% increase relatively. Furthermore, research on traditional HOIP-based SCs is also conducted. Interestingly, the increasing PCE mechanism is quite different from their inorganic counterparts, which should be attributed to the strain effect of different film structures. Thus, the strain-induced defect charge-state transitions of MAPbI3 by the grating layer increased the open-circuit voltage (Voc); and similarly, the increased contacting area also increased the FF, resulting in a 13% increase for PCE.

An improved withdrawal interval calculation and risk assessment of doxycycline in crayfish (Procambarus clarkii) in the natural cultured environment.

Doxycycline is an important medicine in aquaculture for treating fish diseases. However, its excess use causes residue exceeding to threaten human health. So, this study aimed to estimate a reliable withdrawal time (WT) of doxycycline (DC) in crayfish (Procambarus clarkii) based on statistical approaches and conduct a risk assessment for human health in the natural environment. Samples were collected at predetermined time points and determined by high-performance liquid chromatography. A novel statistical method was used to process the data of residue concentration. The homogeneity and linearity of the regressed line of data were evaluated by Bartlett's, Cochran's, and F tests. Outliers were excluded by establishing the standardized residual versus their cumulative frequency distribution on a normal probability scale. The calculated WT was 43 days in muscle of crayfish based on China and European stipulations. After 43 days, estimated daily intakes of DC were ranged from 0.022 to 0.052 µg/kg/d. Hazard Quotients were ranged from 0.007 to 0.014, which were far less than 1. These results indicated that established WT could avoid health risks for humans resulting from DC's residue in crayfish.

Transplantation of Human Amniotic Mesenchymal Stem Cells Up-Regulates Angiogenic Factor Expression to Attenuate Diabetic Kidney Disease in Rats.

Background and Aims: Diabetic kidney disease (DKD) is a prevalent and intractable microvascular complication of diabetes mellitus (DM), the process of which is closely related to abnormal expression of angiogenesis-regulating factors (ARFs). Stem cell transplantation might be a novel strategy for treating DKD. This study aims to explore the effect of transplantation of human amniotic mesenchymal stem cells (hAMSCs) on renal microangiopathy in a type 1 DKD rat model (T1DRM). Methods: Seventy-two rats were randomly divided into three groups, including normal control group, DKD group, and hAMSCs transplantation group. T1DRM was established using a rat tail vein injection of streptozotocin (STZ) (55 mg/kg). hAMSCs were obtained from placental amniotic membranes during cesarean delivery and transplanted at 3 and 4 weeks through penile veins. At 6, 8, and 12 weeks following transplantation, blood glucose levels, renal function, pathological kidney alterations, and the expressions of ARFs' mRNA and protein were analyzed. Results: In T1DRM, transplanted hAMSCs that were homed at the injured site of kidneys increased ARFs' expression and decreased blood glucose levels. Compared to the DKD group, the levels of 24-h urinary protein, serum creatinine, urea, and kidney injury molecule-1 (KIM-1) were reduced in hAMSCs transplantation group. In terms of renal pathology such as the degree of basement membrane thickening, hAMSCs transplantation was also less severe than the DKD group, thereby alleviating kidney injury. Conclusion: hAMSCs transplantation might ameliorate STZ-induced chronic kidney injury through increasing ARFs' expression in kidneys and lowering blood glucose levels.