Shenkang injection for the treatment of acute kidney injury: a systematic review and meta-analysis.

OBJECTIVE: Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the efficacy of Shenkang injection for the treatment of acute kidney injury (AKI). METHODS: A search was conducted across seven databases, encompassing data from the inception of each database through October 8th, 2023. Randomized controlled trials comparing SKI-treated AKI patients with control subjects were extracted. The main outcome measure was serum creatinine (SCr) levels. Secondary outcomes included blood urea nitrogen (BUN), serum cystatin C (CysC), 24-h urine protein (24 h-Upro) levels, APACHE II score and adverse reactions. RESULTS: This meta-analysis included eleven studies, and the analysis indicated that, compared with the control group, SKI significantly decreased SCr [WMD = -23.31, 95% CI (-28.06, -18.57); p < 0.001]; BUN [WMD = -2.07, 95% CI (-2.56, -1.57); p < 0.001]; CysC [WMD = -0.55, 95% CI (-0.78, -0.32), p < 0.001]; 24-h urine protein [WMD = -0.43, 95% CI (-0.53, -0.34), p < 0.001]; and the APACHE II score [WMD = -3.07, 95% CI (-3.67, -2.48), p < 0.001]. There was no difference in adverse reactions between the SKI group and the control group [RR = 1.32, 95% CI (0.66, 2.63), p = 0.431]. CONCLUSION: The use of SKI in AKI patients may reduce SCr, BUN, CysC, 24-h Upro levels, and APACHE II scores in AKI patients. The incidence of adverse reactions did not differ from that in the control group. Additional rigorous clinical trials will be necessary in the future to thoroughly evaluate and establish the effectiveness of SKI in the treatment of AKI.

Differences in Patellofemoral Alignment Between Static and Dynamic Extension Positions in Patients With Patellofemoral Pain.

Background: Considering that patellofemoral pain (PFP) is related to dynamic factors, dynamic extension on 4-dimensional computed tomography (4-DCT) may better reflect the influence of muscles and surrounding soft tissue than static extension. Purpose: To compare the characteristics of patellofemoral alignment between the static and dynamic knee extension position in patients with PFP and controls via 4-DCT. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Included were 39 knees (25 patients) with PFP and 37 control knees (24 participants). For each knee, an image of the dynamic extension position (a single frame of the knee in full extension [flexion angle of -5° to 0°] selected from 21 frames of continuous images acquired by 4-DCT during active flexion and extension) and an image of the static extension position (acquired using the same equipment with the knee fully extended and the muscles relaxed) were selected. Patellofemoral alignment was evaluated between the dynamic and static extension positions and between the PFP and control groups with the following parameters: patella-patellar tendon angle (P-PTA), Blackburne-Peel ratio, bisect-offset (BO) index, lateral patellar tilt (LPT), and tibial tuberosity-trochlear groove (TT-TG) distance. Results: In both PFP patients and controls, the P-PTA, Blackburne-Peel ratio, and BO index in the static extension position were significantly lower (P < .001 for all), while the LPT and TT-TG distance in the static extension position were significantly higher (P ≤ .034 and P < .001, respectively) compared with values in the dynamic extension position. In the comparison between groups, only P-PTA in the static extension position was significantly different (134.97° ± 4.51° [PFP] vs 137.82° ± 5.63° [control]; P = .027). No difference was found in the rate of change from the static to the dynamic extension position of any parameter between the study groups. Conclusion: The study results revealed significant differences in patellofemoral alignment characteristics between the static and dynamic extension positions of PFP patients and controls. Multiplanar measurements may have a role in subsequent patellofemoral alignment evaluation.

3D printed high-precision porous scaffolds prepared by fused deposition modeling induce macrophage polarization to promote bone regeneration.

Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay for cytokine secretion levels.In vitroosteogenic capacity was determined through alkaline phosphatase and alizarin red staining. Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells, exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.

Aggresome formation promotes ASK1/JNK signaling activation and stemness maintenance in ovarian cancer.

Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region. Furthermore, OTUD1-based aggresomes recruit ASK1 via protein-protein interactions, which in turn stabilize ASK1 in a deubiquitinase-independent manner and activate the downstream JNK signaling pathway for OCSC maintenance. Notably, the disruption of OTUD1-based aggresomes or treatment with ASK1/JNK inhibitors, including ibrutinib, an FDA-approved drug that was recently identified as an MKK7 inhibitor, effectively reduced OCSC stemness (OSCS) of OTUD1high ovarian cancer cells. In summary, our work suggests that aggresome formation in tumor cells could function as a signaling hub and that aggresome-based therapy has translational potential for patients with OTUD1high ovarian cancer.

Adaptive bias-variance trade-off in advantage estimator for actor-critic algorithms.

Actor-critic methods are leading in many challenging continuous control tasks. Advantage estimators, the most common critics in the actor-critic framework, combine state values from bootstrapping value functions and sample returns. Different combinations balance the bias introduced by state values and the variance returned by samples to reduce estimation errors. The bias and variance constantly fluctuate throughout training, leading to different optimal combinations. However, existing advantage estimators usually use fixed combinations that fail to account for the trade-off between minimizing bias and variance to find the optimal estimate. Our previous work on adaptive advantage estimation (AAE) analyzed the sources of bias and variance and offered two indicators. This paper further explores the relationship between the indicators and their optimal combination through typical numerical experiments. These analyses develop a general form of adaptive combinations of state values and sample returns to achieve low estimation errors. Empirical results on simulated robotic locomotion tasks show that our proposed estimators achieve similar or superior performance compared to previous generalized advantage estimators (GAE).

Tuning whey protein isolate/hyaluronic acid emulsion gel structure to enhance quercetin bioaccessibility and in vitro digestive characteristics.

Quercetin (Que), a health-promoting polyphenol, has limited applicability in food products due to its susceptibility to degradation in the gastrointestinal tract. To overcome this problem, Que-loaded emulsion gels were produced using whey protein isolate (WPI) and hyaluronic acid (HA) by combining heating and CaCl2 treatment. The effects of HA addition on the structural and rheological properties of the emulsion gels were evaluated, and the protective effect of the gel on Que under simulated digestion was investigated in vitro. Microstructural observations indicated that HA leads to a more compact and uniform network structure, which significantly enhances the textural and rheological properties of emulsion gels. In vitro digestion experiments revealed that WPI-HA emulsion gels exhibited a higher Que bioaccessibility (55.01%) compared to that produced by WPI alone (21.26%). This innovative delivery carrier has potential applications in food products to accomplish sustained nutrient release along with improved stability.

Preparation and characterization of a biocompatible glucose-sensitive electrospun nanofibers scaffolds containing dexamethasone with enhanced osteogenic propertiesin vitrohigh glucose environment.

Diabetes has made it challenging to repair alveolar bone defects. A successful method for bone repair utilizes a glucose-sensitive osteogenic drug delivery. This study created a new glucose-sensitive nanofiber scaffold with controlled dexamethasone (DEX) release. DEX-loaded polycaprolactone/chitosan nanofibers scaffolds were created using electrospinning. The nanofibers had high porosity (>90%) and proper drug loading efficiency (85.51 ± 1.21%). Then, glucose oxidase (GOD) was immobilized on the obtained scaffolds by a natural biological cross-linking agent, genipin (GnP), after soaking in the mixture solution containing GOD and GnP. The enzyme properties and glucose sensitivity of the nanofibers were investigated. The results showed that GOD was immobilized on the nanofibers and exhibited good enzyme activity and stability. Meanwhile, the nanofibers expanded gradually in response to the increase in glucose concentration, followed by the release of DEX increased. The phenomena indicated that the nanofibers could sense glucose fluctuation and possess favorable glucose sensitivity. In addition, the GnP nanofibers group showed lower cytotoxicity in the biocompatibility test compared with a traditional chemical cross-linking agent. Lastly, the associated osteogenesis evaluation found that the scaffolds effectively promoted MC3T3-E1 cells' osteogenic differentiation in high-glucose environments. As a result, the glucose-sensitive nanofibers scaffolds offer a viable treatment option for people with diabetes with alveolar bone defects.

Efficient push-grasping for multiple target objects in clutter environments.

Intelligent manipulation of robots in an unstructured environment is an important application field of artificial intelligence, which means that robots must have the ability of autonomous cognition and decision-making. A typical example of this type of environment is a cluttered scene where objects are stacked and close together. In clutter, the target(s) may be one or more, and efficiently completing the target(s) grasping task is challenging. In this study, an efficient push-grasping method based on reinforcement learning is proposed for multiple target objects in clutter. The key point of this method is to consider the states of all the targets so that the pushing action can expand the grasping space of all targets as much as possible to achieve the minimum total number of pushing and grasping actions and then improve the efficiency of the whole system. At this point, we adopted the mask fusion of multiple targets, clearly defined the concept of graspable probability, and provided the reward mechanism of multi-target push-grasping. Experiments were conducted in both the simulation and real systems. The experimental results indicated that, compared with other methods, the proposed method performed better for multiple target objects and a single target in clutter. It is worth noting that our policy was only trained under simulation, which was then transferred to the real system without retraining or fine-tuning.

The deubiquitinase OTUD1 noncanonically suppresses Akt activation through its N-terminal intrinsically disordered region.

Akt is commonly activated and serves as a valuable target in human cancer. In this study, OTUD1 is identified as an Akt-associated protein and is downregulated upon Akt activation. Ectopic OTUD1 inhibits Akt phosphorylation; however, its deubiquitinase activity contributes only slightly to this effect. A short peptide (OUN-36) located in the OTUD1 N-terminal intrinsically disordered region strongly binds to the Akt PH domain. The residues in the PH domain, which are required for PtdIns(3,4,5)P3 recognition, are also essential for OUN-36 binding. OUN-36 preferentially inhibits Akt-hyperactive tumor cells' proliferation and interferes with Akt cell membrane localization, presumably by disrupting PH domain-PIP3 interaction. Importantly, OUN-36-based therapy efficiently abrogates Akt feedback reactivation in response to MK-2206 treatment and sensitizes cancer cells to chemotherapy and immunotherapy. We therefore show a mechanism by which OTUD1 modulates Akt activity and suggest a potential peptide-based cancer therapeutic strategy implemented by targeting the Akt PH domain.

Neuro- and hepato-toxicity of polystyrene nanoplastics and polybrominated diphenyl ethers on early life stages of zebrafish.

Nanoplastics (NPs) are good carriers of persistent organic pollutants (POPs) such as polybrominated diphenyl ethers (PBDEs) and can modify their bioavailability and toxicity to aquatic organisms. This study highlights the single and combined toxic effects of polystyrene nanoplastics (PS-NPs) and 2,2 ',4,4 '-tetrabromodiphenyl ether (BDE-47, one of the major PBDE congeners) on zebrafish embryos after an exposure of up to 120 hpf. Our results showed that PS-NPs and BDE-47 formed larger particle aggregates during co-exposure, which attached to the surface of the yolk membrane and even changed its structure, and these particles also bioaccumulated in the intestine of zebrafish larvae, compared with the PS-NPs single exposure. Further, the co-exposure significantly increased mortality, accelerated voluntary movements, enhanced hatching rate, and decreased heart rate. Hepatoxicity analyses revealed that the mixture exposure induced a darker/browner liver colour, atrophied liver and greater hepatotoxicity in zebrafish larvae. In addition to increased ROS accumulation, the reduced expression of the antioxidant gpx1a gene and increased expression of cyp1a1 were found after co-treatment. Moreover, ache and chrn7α genes associated with neurocentral development, were significantly downregulated, mainly in the co-exposure group. In conclusion, simultaneous exposure to PS-NPs and BDE-47 exacerbated oxidative stress, developmental impacts, hepatotoxicity, and neurodevelopmental toxicity in zebrafish larvae. Therefore, neurotoxic effects of complex chemical interactions between PS-NPs and persistent organic pollutants in freshwater environments should be paid more attention.

Improving Mechanical, Electrical and Thermal Properties of Fluororubber by Constructing Interconnected Carbon Nanotube Networks with Chemical Bonds and F-H Polar Interactions.

To improve the properties of fluororubber (FKM), aminated carbon nanotubes (CNTs-NH2) and acidified carbon nanotubes (CNTs-COOH) were introduced to modulate the interfacial interactions in FKM composites. The effects of chemical binding and F-H polar interactions between CNTs-NH2, CNTs-COOH, and FKM on the mechanical, electrical, thermal, and wear properties of the FKM composites were systematically investigated. Compared to the pristine FKM, the tensile strength, modulus at 100% strain, hardness, thermal conductivity, carbon residue rate, and electrical conductivity of CNTs-NH2/CNTs-COOH/FKM were increased by 112.2%, 587.5%, 44.2%, 37.0%, 293.5%, and nine orders of magnitude, respectively. In addition, the wear volume of CNTs-NH2/CNTs-COOH/FKM was reduced by 29.9%. This method provides a new and effective way to develop and design high-performance fluororubber composites.

Tuberculous Thoracic Aortic Pseudoaneurysm Associated With Spinal Tuberculosis: A Case Report and Literature Review.

Background: Thoracic aortic pseudoaneurysm associated with spinal tuberculosis is a rare but fatal condition. The risk of pseudoaneurysm rupture is extremely high and this disease needs greater awareness. The present study reported a case of thoracic aortic pseudoaneurysm caused by paravertebral cold abscess with spinal tuberculosis. Case presentation: A 35-year-old woman with back pain was diagnosed with thoracic aortic pseudoaneurysm with spinal tuberculosis, and endovascular aneurysm repair (EVAR) was performed. The patient's symptoms disappeared after EVAR, following which she was discharged. Conclusions: The case highlighted that in cases where non-enhanced computed tomography (CT) revealed that the aortic vessel was surrounded by a paravertebral abscess, magnetic resonance imaging (MRI) should be performed to confirm whether the presence of a pseudoaneurysm. Upon diagnosis of pseudoaneurysm, surgery should be performed immediately. In recent times, EVAR has emerged as a promising alternative to open surgery.

Effects of high-hydrostatic pressure and high-pressure homogenization on the biological activity of cabbage dietary fiber.

BACKGROUND: Cabbage is one of the most economical cooked vegetables in terms of its relatively low price and high nutritional value. It is rich in dietary fiber, multivitamins, and a variety of anti-oxidants. In this study, we compared the effects of high-hydrostatic pressure (HHP) and high-pressure homogenization (HPH) treatments on changes in composition and physiological functions of cabbage dietary fiber. RESULTS: The total dietary fiber content (36.06 ± 1.65%) and nitrite ion adsorption capacity (2.37 ± 0.01 µmol·g-1 ) of HHP-treated cabbage powder were higher than those of untreated cabbage powder. The soluble dietary fiber content (36.18 ± 0.89%) and the emulsifying activity (36.18 ± 0.89%) and emulsifying stability (47.88 ± 4.35%) of HPH-treated cabbage powder were higher than those of untreated cabbage powders. The significant reduction in particle size induced by the high-pressure treatments caused differences in the properties of the treated and untreated cabbage powder samples. Scanning electronic microscopy analysis revealed that the microstructure of the HPH-treated cabbage powder changed from patches to fine granules with concave-convex markings on the surface, and that the surface area was significantly higher than that of the untreated cabbage powder. The high-pressure-treated cabbage powder has good homogeneity sensory properties after rehydration. Moreover, the changes in the properties of cabbage powder induced by the high-pressure treatments caused the cholesterol adsorption capacity and glucose dialysis retardation index of the treated cabbage powders to be higher than those of the untreated cabbage powder. CONCLUSION: In summary, high-pressure processing and micronization of cabbage can render it a multifunctional source of dietary fiber. We believe that this study provides a new method for processing and using leftover vegetables. © 2022 Society of Chemical Industry.

Toxic effects of polystyrene nanoplastics and polybrominated diphenyl ethers to zebrafish (Danio rerio).

Nanoplastics (NPs) are good carriers of persistent organic pollutants (POPs) such as polybrominated diphenyl ethers (PBDEs), and can alter their bioavailability and toxic impacts to aquatic organisms. This study highlights the single and combined toxic effects of polystyrene nanoplastics (PS-NPs) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, one of the dominant congeners of PBDEs) on zebrafish embryos after an exposure duration of up to 120 hpf. Results showed that PS-NPs and BDE-47 co-exposure exacerbated the morphological deformities in terms of pericardial edema, yolk sac edema and curved tail in zebrafish larvae. Compared to BDE-47 single exposure, the combined exposure caused lower survival rates, shorter body lengths, and accelerated spontaneous movements. Further, PS-NPs were quickly aggregated on the surface of the embryonic chorions covered almost the entire membrane at 12 and 48 hpf, and concentration dependent accumulation was also found in the brain, mouth, trunk, gills, heart, liver and gastrointestinal tract at the larval stages. During the recovery period (7 days), PS-NPs were released from all the organs, with the highest elimination from the gastrointestinal tract. Histopathological examination revealed that co-exposure caused greater damage to retinal structures, muscle fibers and cartilage tissues. Responses of hypothalamic-pituitary-thyroid axis (CRH, TSHß, NIS, TTR, Dio2, TG, TRα and TRß) and reproduction (Esr2 and Vtg1) related genes were also investigated, and results showed that the co-exposure induced more significant upregulated expressions of TSHß, TG, Doi 2, and TRß, compared to BDE-47 single exposure. In conclusion, co-exposure to NPs and BDE-47 exacerbated developmental and thyroid toxicity in zebrafish, generally elucidating the toxicological effects mediated by complex chemical interactions between NPs with POPs in the freshwater environment.

A clinical randomized controlled trial: moxibustion at Laogong interval with Panax notoginseng promoted the maturation of arteriovenous fistulae.

BACKGROUND: We aim to study the clinical effect of moxibustion at Laogong interval with Panax notoginseng on the short-term maturation and long-term patency of arteriovenous fistula. METHODS: Seventy-four pre-dialysis uremic patients who received distal forearm radial-cephalic fistula creations were enrolled in this study and randomly assigned to the control group and experimental group. After arteriovenous fistula creations, the control group underwent handgrip exercise, and the experimental group received moxibustion at Laogong acupoint interval with Panax notoginseng. Both groups received a 12-week treatment and were followed up for 24 weeks in all at the following time points: before creations and 2, 4, 8, 12, 24 weeks after creations. The diameter of anastomosis, the diameter and outflow of draining-veins 5 cm above anastomosis, the diameter and outflow of brachial arteries evaluated the maturation and patency of arteriovenous fistula. Enzyme linked immunosorbent assay determined serum levels of endothelin and nitric oxide. RESULTS: The maturity rate in the experimental group was significantly higher than that in the control group at 4 weeks after arteriovenous fistula creations (P = 0.048). The diameter of anastomosis, the diameter of draining veins, and the blood flow of draining veins increased in both groups during the whole 24 weeks. The diameter and blood flow of brachial arteries ascended in both groups during the previous 12 weeks. Compared with the control group, moxibustion at Laogong interval with Panax notoginseng significantly improved the value of the diameter of draining-veins (P = 0.016), the blood flow of draining-veins (P = 0.015), the diameter of brachial arteries (P < 0.001), and the blood flow of brachial arteries (P = 0. 012) at 2 weeks, and enhanced the blood flow of draining-veins (P = 0.029) and brachial arteries (P < 0.001) at 12 weeks. Serum levels of endothelin were significantly lower (P = 0.047), and serum levels of nitric oxide were markedly higher (P < 0.001) in the experimental group than that in the control group at 2 weeks after creations. CONCLUSIONS: Moxibustion at Laogong interval with Panax notoginseng was non-invasive and promoted the maturation of arteriovenous fistula at 4 weeks after creations. However, its long-term beneficial effect on patency at 24 weeks after creations was not significant. Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024042. Registered, http://www.chictr.org.cn/index.aspx.

Cancer-Erythrocyte Hybrid Membrane-Camouflaged Magnetic Nanoparticles with Enhanced Photothermal-Immunotherapy for Ovarian Cancer.

Cell-membrane-coated nanoparticles are widely studied due to their inherent cellular properties, such as immune escape and homologous homing. A cell membrane coating can also maintain the relative stability of nanoparticles during circulation in a complex blood environment through cell membrane encapsulation technology. In this study, we fused a murine-derived ID8 ovarian cancer cell membrane with a red blood cell (RBC) membrane to create a hybrid biomimetic coating (IRM), and hybrid IRM camouflaged indocyanine green (ICG)-loaded magnetic nanoparticles (Fe3O4-ICG@IRM) were fabricated for combination therapy of ovarian cancer. Fe3O4-ICG@IRM retained both ID8 and RBC cell membrane proteins and exhibited highly specific self-recognition of ID8 cells in vitro and in vivo as well as a prolonged circulation lifetime in blood. Interestingly, in the bilateral flank tumor model, the IRM-coated nanoparticles also activated specific immunity, which killed homologous ID8 tumor cells but had no effect on B16-F10 tumor cells. Furthermore, Fe3O4-ICG@IRM showed synergistic photothermal therapy, resulting in the release of whole-cell tumor antigens by photothermal-induced tumor necrosis, which further enhanced antitumor immunotherapy for primary tumor and metastatic tumor by activating CD8+ cytotoxic T cells and reducing regulatory Foxp3+ T cells. Together, the biomimetic Fe3O4-ICG@IRM nanoparticles showed synergistic photothermal-immunotherapy for ovarian cancer.

Deficiency of the X-inactivation escaping gene KDM5C in clear cell renal cell carcinoma promotes tumorigenicity by reprogramming glycogen metabolism and inhibiting ferroptosis.

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by glycogen-laden, unexplained male predominance, and frequent mutations in the Von Hippel-Lindau (VHL) gene and histone modifier genes. Besides, poor survival rates of ccRCC patients seem to be associated with up-regulation of the pentose phosphate pathway (PPP). However, the mechanism underlying these features remains unclear. Methods: Whole exome sequencing was used to identify the gene mutation that implicated in the rewired glucose metabolism. RNA-seq analyses were performed to evaluate the function of KDM5C in ccRCC. Furthermore, heavy isotope tracer analysis and metabolites quantification assays were used to study how KDM5C affects intracellular metabolic flux. To provide more in vivo evidence, we generated the Kdm5c-/- mice by CRISPR-Cas9 mediated gene knockout and performed the xenografts with KDM5C overexpressing or depleted cell lines. Results: A histone demethylase gene KDM5C, which can escape from X-inactivation and is predominantly mutated in male ccRCC patients, was identified to harbor the frameshift mutation in the ccRCC cell line with the highest glycogen level, while the restoration of KDM5C significantly reduced the glycogen level. Transcriptome and metabolomic analysis linked KDM5C to metabolism-related biological processes. KDM5C specifically regulated the expression of several hypoxia-inducible factor (HIF)-related genes and Glucose-6-phosphate dehydrogenase (G6PD) that were involved in glycogenesis/glycogenolysis and PPP, respectively, mainly through the histone demethylase activity of KDM5C. Depletion of KDM5C increased the production of glycogen, which was then directed to glycogenolysis to generate glucose-6-phosphate (G6P) and subsequently PPP to produce nicotinamide adenine dinucleotide phosphate hydride (NADPH) and glutathione (GSH), thus conferring cells resistance to reactive oxygen species (ROS) and ferroptosis. KDM5C re-expression suppressed the glucose flux through PPP and re-sensitized cancer cells to ferroptosis. Notably, Kdm5c-knockout mice kidney tissues exhibited elevated glycogen level, reduced lipid peroxidation and displayed a transformation of renal cysts into hyperplastic lesions, implying a cancer-protective benefit of ferroptosis. Furthermore, KDM5C deficiency predicted the poor prognosis, and clinically relevant KDM5C mutants failed to suppress glycogen accumulation and promoted ferroptosis as wild type. Conclusion: This work revealed that a histone modifier gene inactive mutation reprogramed glycogen metabolism and helped to explain the long-standing puzzle of male predominance in human cancer. In addition, our findings may suggest the therapeutic value of targeting glycogen metabolism in ccRCC.

Potential mechanism of RRM2 for promoting Cervical Cancer based on weighted gene co-expression network analysis.

Cervical cancer is the most common gynecologic malignant tumor, with a high incidence in 50-55-year-olds. This study aims to investigate the potential molecular mechanism of RRM2 for promoting the development of cervical cancer based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). RRM2 was found to be significant upregulated in cervical tissue (P<0.05) by extracting the expression of RRM2 from TCGA, GSE63514, GSE7410, GSE7803 and GSE9750. Survival analysis indicated that the overall survival was significantly worse in the patients with high-expression of RRM2 (P<0.05). The top 1000 positively/negatively correlated genes with RRM2 by Pearson Correlation test were extracted. The gene co-expression network by Weighted Gene Co-Expression Network Analysis (WGCNA) with these genes and the clinical characteristics (lymphocyte infiltration, monocyte infiltration, necrosis, neutrophil infiltration, the number of normal/stromal/tumor cells and the number of tumor nuclei) was constructed. By screening the hub nodes from the co-expression network, results suggested that RRM2 may co-express with relevant genes to regulate the number of stromal/tumor cells and the process of lymphocyte infiltration to promote the progression of cervical cancer. RRM2 is likely to become a novel potential diagnostic and prognostic biomarker of cervical cancer and provide evidence to support the study of mechanisms for cervical cancer.

A potential drug combination of omeprazole and patchouli alcohol significantly normalizes oxidative stress and inflammatory responses against gastric ulcer in ethanol-induced rat model.

Omeprazole (OME) is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, OME may cause some inevitable side effects and the long-term consequences of OME could increase the risk of diarrhea. Patchouli Alcohol (PA), the main extract of Pogostemonis Herba, have demonstrated benefits in treating gastric ulcer (GU) with low toxicity. The present study aimed to investigate the synergistically protective effects of OME and PA against ethanol-induced GU in rats to study the involvement of antioxidant and anti-inflammatory activities. Moreover, the anti-apoptosis, anti-oxidant and anti-inflammatory effects in H2O2-induced gastric epithelial cells (GES-1) and LPS-induced RAW264.7 cells were determined, as well as the modulation of signaling proteins. The results demonstrated that PA alone or combined with OME provided remarkable benefits by reducing ulcer areas, modulating oxidant stress and inflammatory factors and the therapeutic efficacy was showed to be dose-dependent, which were partly superior to that of high-dose OME only. Additionally, co-treated regimen could superiorly down-regulate cell apoptosis and regulate the levels of oxidant activities and inflammatory cytokines on H2O2-induced GES-1 cells and LPS-induced RAW264.7 cells, which involved with cleaved caspase 3, Bcl-2 and BAX protein expressions and MAPK pathway. We provided a new understanding that the combination of OME and PA possessed gastroprotective effects on modulating cell apoptosis, antioxidant stress and anti-inflammatory responses against GU. Therefore, PA was inferred to take a potential and critic role in gastric mucosa protection.

The New Biomarker for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Based on Public Database Mining.

To reconstruct the ceRNA biological network of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and to select an appropriate mRNA as a biomarker that could be used for CESC early diagnosis and prognosis evaluation. We downloaded CESC data from the TCGA public database, and statistical analysis was conducted with the R software to find out differential expressed genes encoding for lncRNAs, miRNAs, and mRNAs. The differentially expressed mRNAs (DEmRNAs) screened in the ceRNA network were analyzed for survival to find the mRNAs with significantly linked to the survival prognosis. These mRNAs were searched in the Pathological Atlas to identify the final appropriate mRNAs. Differential expression analysis revealed 773 lncRNAs, 94 miRNAs, and 2466 mRNAs. Survival analysis of DEmRNAs in the ceRNA network indicated that ADGRF4, ANXA8L1, HCAR3, IRF6, and PDE2A (P < 0.05) were negatively correlated with survival time. Verification of these six DEmRNAs in the Pathology Atlas indicated that PDE2A was a possible biomarker for CESC patients. PDE2A might be a biomarker for early diagnosis and prognosis evaluation of CESC patients, but due to the lack of available data, further studies may be needed for confirmation.