ABSTRACT
BACKGROUND: Understanding the relationship between human evolution and environmental changes is the key to lifting the veil on human origin. The hypothesis that environmental changes triggered the divergence of humans from apes (ca. 9.3-6.5 million years ago, Ma) has been poorly tested because of limited continuous environmental data from fossil localities. Lufengpithecus (12.5-6.0 Ma) found on the southeastern margin of the Tibetan Plateau (SEMTP) across the ape-human split provides a good chance for testing this hypothesis. RESULTS: Here, we reconstructed the habitats of L. keiyuanensis (12.5-11.6 Ma) with comprehensive vegetation, climate, and potential food web data by palaeobotanical evidence, together with other multidisciplinary data and partly tested the environment-driven hypothesis by revealing the living conditions of Lufengpithecus. CONCLUSION: A detailed comparison of hominoids on different continents reveals their behaviour and fate divergence across the ape-human split against the background of global climate change, i.e., the stable living conditions of SEMTP not only provided a so-called 'refuge' for arboreal Lufengpithecus but also acted as a 'double-edged sword', preventing their further evolution while vegetation shifts in East Africa probably stimulated the emergence of human bipedalism, and the intense climatic changes in Europe possibly prevented those hominoids from surviving that time interval. Our findings provide interesting insight into the environmental impacts on the behavioural evolution of hominoids.
Subject(s)
Hominidae , Social Conditions , Animals , Humans , Phylogeny , Asia, Eastern , Fossils , Biological EvolutionABSTRACT
BACKGROUND: Chimeric antigen receptor (CAR)-T-cell therapy is a revolutionary treatment that has become a mainstay of advanced cancer treatment. Conventional glypican-3 (GPC3)-CAR-T cells have not produced ideal clinical outcomes in advanced hepatocellular carcinoma (HCC), and the mechanism is unclear. This study aims to investigate the clinical utility of novel GPC3-7-19-CAR-T cells constructed by our team and to explore the mechanisms underlying their antitumor effects. METHODS: We engineered a novel GPC3-targeting CAR including an anti-GPC3 scFv, CD3ζ, CD28 and 4-1BB that induces co-expression of IL-7 at a moderate level (500 pg/mL) and CCL19 at a high level (15000 pg /mL) and transduced it into human T cells. In vitro, cell killing efficacy was validated by the xCELLigence RTCA system, LDH nonradioactive cytotoxicity assay and was confirmed in primary HCC organoid models employing a 3D microfluid chip. In vivo, the antitumor capacity was assessed in a humanized NSG mouse xenograft model. Finally, we initiated a phase I clinical trial to evaluate the safety and effect of GPC3-7-19-CAR-T cells in the clinic. RESULTS: GPC3-7-19-CAR-T cells had 1.5-2 times higher killing efficiency than GPC3-CAR-T cells. The tumor formation rates in GPC3-7-19-CAR-T cells treated model were reduced (3/5vs.5/5), and the average tumor volumes were 0.74 cm3 ± 1.17 vs. 0.34 cm3 ± 0.25. Of note, increased proportion of CD4+ TEM and CD8+ TCM cells was infiltrated in GPC3-7-19-CAR-T cells group. GPC3-7-19-CAR-T cells obviously reversed the immunosuppressive tumor microenvironment (TME) by reducing polymorphonuclear (PMN)-myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells infiltration and recruiting more dendritic cells (DCs) to HCC xenograft tumor tissues. In one patient with advanced HCC, GPC3-7-19-CAR-T-cell treatment resulted in tumor reduction 56 days after intravenous infusion. CONCLUSIONS: In conclusion, GPC3-7-19-CAR-T cells achieved antitumor effects superior to those of conventional GPC3-CAR-T cells by reconstructing the TME induced by the dominant CD4+ TEM and CD8+ TCM cell subsets. Most importantly, GPC3-7-19-CAR-T cells exhibited good safety and antitumor efficacy in HCC patients in the clinic. ⺠Novel GPC3-7-19-CAR-T cells designed with mediate level of IL-7 secretion and high level of CCL19 secretion, which could recruit more mature DCs to assist killing on GPC3+HCCs. âºDC cells recruited by CCL19 could interact with CD4+ T cells and promote the differentiation of CD4+TEFF cells into CD4+TEM and CD8+TCM subsets, leading a better anti-tumor effect on GPC3+HCCs. âºCompared with conventional GPC3-CAR-T, GPC3-7-CCL19-CAR-T cells could reverse tumor immunosuppressive microenvironment by reducing PMN-MDSC and Treg cell infiltration.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Receptors, Chimeric Antigen , Humans , Animals , Mice , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Interleukin-7 , Glypicans , Cell Line, Tumor , Tumor Microenvironment , Chemokine CCL19ABSTRACT
KEY MESSAGE: GhSCL13-2A, a member of the PAT1 subfamily in the GRAS family, positively regulates cotton resistance to Verticillium dahliae by mediating the jasmonic acid and salicylic acid signaling pathways and accumulation of reactive oxygen species. Verticillium wilt (VW) is a devastating disease of upland cotton (Gossypium hirsutum) that is primarily caused by the soil-borne fungus Verticillium dahliae. Scarecrow-like (SCL) proteins are known to be involved in plant abiotic and biotic stress responses, but their roles in cotton defense responses are still unclear. In this study, a total of 25 GhPAT1 subfamily members in the GRAS family were identified in upland cotton. Gene organization and protein domain analysis showed that GhPAT1 members were highly conserved. GhPAT1 genes were widely expressed in various tissues and at multiple developmental stages, and they were responsive to jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) signals. Furthermore, GhSCL13-2A was induced by V. dahliae infection. V. dahliae resistance was enhanced in Arabidopsis thaliana by ectopic overexpression of GhSCL13-2A, whereas cotton GhSCL13-2A knockdowns showed increased susceptibility. Levels of reactive oxygen species (ROS) and JA were also increased and SA content was decreased in GhSCL13-2A knockdowns. At the gene expression level, PR genes and SA signaling marker genes were down-regulated and JA signaling marker genes were upregulated in GhSCL13-2A knockdowns. GhSCL13-2A was shown to be localized to the cell membrane and the nucleus. Yeast two-hybrid and luciferase complementation assays indicated that GhSCL13-2A interacted with GhERF5. In Arabidopsis, V. dahliae resistance was enhanced by GhERF5 overexpression; in cotton, resistance was reduced in GhERF5 knockdowns. This study revealed a positive role of GhSCL13-2A in V. dahliae resistance, establishing it as a strong candidate gene for future breeding of V. dahliae-resistant cotton cultivars.
Subject(s)
Ascomycota , Verticillium , Gossypium/metabolism , Reactive Oxygen Species/metabolism , Plant Breeding , Verticillium/physiology , Salicylic Acid/metabolism , Disease Resistance/genetics , Plant Diseases/genetics , Plant Diseases/microbiology , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Lead (Pb) is a corrosion-resistant, heavy, non-ferrous metal. Several metal chelators have been used for the treatment of Pb poisoning. However, the efficacy of sodium para-aminosalicylic acid (PAS-Na) in enhancing Pb excretion has yet to be fully characterized. Healthy male mice (90) were divided into six groups, the normal control group was intraperitoneally (i.p.) injected with saline and the remaining group of mice i.p. 120 mg/kg Pb acetate. Four hour later, mice were subcutaneously (back) injected (s.c.) with (80, 160, 240 mg/kg) PAS-Na or 240 mg/kg edetate calcium disodium (CaNa2EDTA) or an equivalent amount of saline, once per day for 6 days. After 24-h urine sample collections, the animals were anesthetized with 5% chloral hydrate and sacrificed in batches on the 2nd, 4th, or 6th day. Levels of Pb [including manganese (Mn) and copper (Cu)] in the urine, whole blood, and brain tissues were analyzed by graphite furnace atomic absorption spectrometry. The results showed that Pb exposure increased its levels in urine and blood, and PAS-Na treatment may afford antagonistic effect on Pb poisoning, suggesting that PAS-Na is a potentially effective treatment to promote excretion of Pb.
Subject(s)
Aminosalicylic Acid , Rats , Male , Mice , Animals , Aminosalicylic Acid/therapeutic use , Aminosalicylic Acid/pharmacology , Rats, Sprague-Dawley , Lead/toxicity , Sodium , Chelating Agents/pharmacology , Chelating Agents/therapeutic useABSTRACT
The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl2) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl2. After adaptive feeding for 7 days, male and female Sprague-Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl2·4H2O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT's propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl2-treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl2 groups. In summary, these findings suggest that MMT and MnCl2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl2's manifestations of atypical parkinsonism.
Subject(s)
Manganese Poisoning , Manganese , Animals , Chlorides , Female , Male , Manganese/toxicity , Manganese Compounds , Rats , Rats, Sprague-Dawley , Substantia NigraABSTRACT
Hong Kong oyster (Crassostrea hongkongensis) is one of the main species of economic shellfish cultivated in the coastal areas of southern China. The cultivation of this shellfish may be adversely impacted by Vibrio parahaemolyticus, a harmful pathogenic bacterium for many mariculture species, as it usually exists on the surface of Hong Kong oysters. Although previous studies have discovered that oysters rely on non-specific immune system to fight pathogen invasion, the genes corresponding to the complex immune system against Vibrio is still not fully elucidated. Therefore, we conducted a transcriptome analysis on the gill from Hong Kong oysters at two time points (i.e., 12 h and 24 h after V. parahaemolyticus or PBS challenge) to identify potential immune genes against V. parahaemolyticus infection. A total of 61779 unigenes with the average length of 1221 bp were obtained, and the annotation information of 39917 unigenes were obtained from Nr, SwissProt, KEGG and COG/KOG. After a pairwise comparison between V. parahaemolyticus or PBS challenge at the two time points, three groups of differentially expressed genes induced by V. parahaemolyticus were captured and analyzed. GO and KEGG analyses showed that multiple immune-related genes played an important role in pathogen infection, including HSP70, PCDP3 and TLR4. Furthermore, genes annotation indicated that LITAF, TNFSF10, Duox2 and big defensin family are also involved in immune regulation. Our study provides a reference for further exploration the molecular mechanism that defenses the pathogen infection regarding the identified immune-related genes in Hong Kong oysters.
Subject(s)
Crassostrea , Vibrio Infections , Vibrio parahaemolyticus , Animals , Gene Expression Profiling , Hong Kong , Vibrio Infections/microbiology , Vibrio Infections/veterinary , Vibrio parahaemolyticus/physiologyABSTRACT
Despite that the currently discovered CRISPR-Cas12a system is beneficial for improving the detection accuracy and design flexibility of luminescent biosensors, there are still challenges to extend target species and strengthen adaptability in complicated biological media. To conquer these obstacles, we present here some useful strategies. For the former, the limitation to nucleic acids assay is broken through by introducing a simple functional DNA regulation pathway to activate the unique trans-cleavage effect of this CRISPR system, under which the expected biosensors are capable of effectively transducing a protein (employing dual aptamers) and a metal ion (employing DNAzyme). For the latter, a time-gated luminescence resonance energy transfer imaging manner using a long-persistent nanophosphor as the energy donor is performed to completely eliminate the background interference and a nature-inspired biomimetic periodic chip constructed by photonic crystals is further combined to enhance the persistent luminescence. In line with the above efforts, the improved CRISPR-Cas12a luminescent biosensor not only exhibits a sound analysis performance toward the model targets (carcinoembryonic antigen and Na+) but also owns a strong anti-interference feature to actualize accurate sensing in human plasma samples, offering a new and applicative analytical tool for laboratory medicine.
Subject(s)
Biosensing Techniques , DNA, Catalytic , Biomimetics , CRISPR-Cas Systems/genetics , DNA/genetics , Humans , LuminescenceABSTRACT
Human sparganosis is a food-borne parasitic disease caused by the plerocercoids of Spirometra species. Clinical diagnosis of sparganosis is crucial for effective treatment, thus it is important to identify sensitive and specific antigens of plerocercoids. The aim of the current study was to identify and characterize the immunogenic proteins of Spirometra erinaceieuropaei plerocercoids that were recognized by patient sera. Crude soluble extract of the plerocercoids were separated using 2-dimensional gel electrophoresis coupled with immunoblot and mass spectrometry analysis. Based on immunoblotting patterns and mass spectrometry results, 8 antigenic proteins were identified from the plerocercoid. Among the proteins, cysteine protease protein might be developed as an antigen for diagnosis of sparganosis.
Subject(s)
Sparganosis , Spirometra , Animals , Electrophoresis, Gel, Two-Dimensional , Humans , Immunoblotting , Proteomics , Sparganosis/diagnosisABSTRACT
We developed a new method for chiral separation of fourteen amino alcohols by nonaqueous capillary electrophoresis (NACE) with the D-(+)-gluconic acid δ-lactone-boric acid complex as chiral selector. In order to achieve good enantioseparation, the effects of D-(+)-gluconic acid δ-lactone and boric acid concentrations, triethylamine concentration, as well as capillary temperature were systematically investigated. The optimized conditions were identified as follows: an uncoated fused silica capillary of 50 µm ID with a total length (L(tot)) of 55 cm and an effective length (L(eff)) of 45 cm; 200 mmol·L(-1) D-(+)-gluconic acid δ-lactone, 80 mmol·L(-1) boric acid, and 57.4 mmol·L(-1) triethylamine in methanol; positive pressure injection at 2.9 psi for 2 s; capillary temperature, 25 ± 0.2 â; applied voltage, +15 k V; detection wavelength, 214 nm. Under the optimized conditions, a good chiral resolution was achieved in most of the tested drugs. This method provides a foundation for the development and application of new chiral selectors of polyhydroxy compound-boric acid complexes in chiral drugs analysis by NACE.
Subject(s)
Amino Alcohols/isolation & purification , Electrophoresis, Capillary , Boric Acids/chemistry , Ethylamines/chemistry , Hydrogen-Ion Concentration , Stereoisomerism , TemperatureABSTRACT
We report here the NHC-Pd(II)-Im complex 1-catalyzed direct C-H bond functionalization of the C9 position of fluorenes with aryl chlorides and further transformation of the resulting products in a one-pot procedure. Under the optimal conditions, arylated fluorenes can be obtained in moderate to almost quantitative yields using various activated and unactivated (hetero)aryl chlorides as the arylating reagents. Furthermore, if the mixture from the arylation reaction is exposed to air, the C9-oxidized products can be obtained in acceptable to good yields in a one-pot procedure. In addition, alkyl groups can also be efficiently introduced to the above mixture from the arylation reaction, producing further C9-alkylated products in good to almost quantitative yields in a one-pot procedure, thus providing an expedient, inexpensive and practical strategy for the mono- and di-functionalization of fluorenes.
ABSTRACT
Lung cancer is the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most common type, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of NSCLC. EGFR-TKIs are known to develop a drug-resistant response after a certain number of cycles of dosing, and how to alleviate or even reverse EGFR-TKI resistance is an urgent problem at present. This review focuses on the role of ncRNAs in the resistance of NSCLC to EGFR-TKIs and the potential mechanisms underlying the development of NSCLC resistance to EGFR-TKIs. NcRNAs are involved in NSCLC resistance to EGFR-TKIs by mediating cellular drug efflux, epithelial-mesenchymal transition, apoptosis, autophagy, and EGFR mutation. ncRNAs play a crucial role in NSCLC resistance to EGFR-TKIs. Hopefully, the results will provide some guidance and help for the treatment and prognosis of NSCLC.
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Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations.
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OBJECTIVE: To analysis the differential expression of decidua tissue proteins and effective mechanisms of recurrent abortion mice with Shoutai Wan, and explore the mechanism of Shoutai Wan in preventing miscarriage. METHOD: The abortion-prone CBA/J x DBA/2 matings were established as the model of recurrent abortion and the nonabortion-prone CBA/J x BALB/c matings were used as the model of normal pregnancy. The model of recurrent abortion CBA/J x DBA/2 of mice pregnant were randomly divided into four groups according to the sequence of pregnancy, including model group, Shoutai Wan low-dose group, Shoutai Wan middle-dose group and Shoutai Wan high-dose group. From the 1st day of pregnant, mice of normal group, model group, Shoutai Wan low-dose group (3 g x kg x d(-1)), Shoutai Wan middle-dose group (6 g x kg x d(-1)) and Shoutai Wan high-dose group (12 g x kg x d(-1)) are oral administration in different doses. On the 14th day of pregnancy, all mice are killed and the embryo loss rate (ELR) was counted. The expression of differential proteins of mice decidua tissues were separated by means of 2-DE and identified by MALDI-TOF-MS. The functions of identified proteins were further analysed according to bioinformatics resources. RESULT: Compared with model group, low-dose Shoutai Wan can not significantly improve the model of recurrent abortion in pregnant mice ELR; Shoutai Wan middle-dose and high-dose group of pregnant mice ELR were significantly decreased (P < 0.01). The results showed that the well-resolved, reproducible 2-DE patterns of mice decidua tissues of model group, normal group and Shoutai Wan low middle high-dose group were obtained. Through comparative proteome analysis of decidua tissues of all groups, 30 differential expression protein spots which maybe related to recurrent abortion and Shoutai Wan intervention were identified by MALDI-TOF-MS. These differential expression proteins mainly refer to invasion of the blastocyst, blood vessel remodeling and cell apoptosis. CONCLUSION: Shoutai Wan can decrease recurrent abortion mice ELR significantly, and play a role in preventing miscarriage. Recurrent abortion is a complicated process refer to diverse proteins participate. For several protein spots expression of decidua tissues in recurrent abortion mice was regulated by Shoutai Wan, it provides contribution to the effect characteristic of multitarget.
Subject(s)
Abortion, Habitual/metabolism , Abortion, Habitual/prevention & control , Decidua/drug effects , Decidua/metabolism , Drugs, Chinese Herbal/pharmacology , Proteome/metabolism , Abortion, Habitual/pathology , Animals , Decidua/pathology , Female , Mice , PregnancyABSTRACT
BACKGROUND: Accumulating evidences have demonstrated that overwhelming inflammation occurs in the process of Coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVM). No specific therapy is available. More than an effective Janus-associated kinase (JAK) inhibiter, ruxolitinib exerts a critical role in the inflammatory diseases. In this study, we investigated the potential effect of ruxolitinib on CVB3-induced acute viral myocarditis. METHOD: In vivo, BALB/c mice were intraperitoneally injected of CVB3, treated of a successive gavage of ruxolitinib for seven days, and subjected to a series of analysis. In vitro, primary bone marrow-derived macrophages (BMDMs) and cardiac fibroblasts were isolated, cultured, treated, harvested and finally detected. RESULTS: In vivo, acute viral myocarditis was successfully induced by the injection of CVB3 characterized by impaired cardiac function, predominant infiltration of inflammatory cells, necroptosis of myocardium, great increase of cardiac troponin I (cTnI) and cytokine levels, replication of CVB3, and excessive activation of JAK-STAT pathways. Oral administration of ruxolitinib suppressed the activation of JAK-STAT pathway in a dosage-dependent way, lessened the infiltration of inflammatory cells and necroptosis of myocardium, reduced the levels of cTnI and cytokines, and finally alleviated CVB3-induced cardiac dysfunction, with the reduced production of type I interferon and no promising effect on the replication of CVB3. In vitro, the treatment of ruxolitinib inhibited the activation of JAK-STAT pathway and increase of multiple cytokines mRNA levels in BMDMs and had no protective effect against CVB3 replication in cardiac fibroblasts. CONCLUSIONS: Our study suggested that ruxolitinib ameliorated CVB3-induced AVM by inhibiting the activation of JAK-STAT pathway, infiltration of inflammatory cells and necroptosis of myocardium, which may provide a novel strategy for AVM therapy.
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Phenanthrene (Phe), a typical polycyclic aromatic hydrocarbon (PAH) pollutant, poses an enormous safety risk to rice-crab coculture (RC) paddy ecosystems. In this study, humic acid-modified purified attapulgite (HA-ATP) with a composite structure was successfully fabricated to adsorb PAHs released from paddy soil to overlying water in RC paddy ecosystems in Northeast China. The maximum crab bioturbation intensities for dissolved Phe and particulate Phe were 64.83nullng/L·(cm2·d) and 214.29nullng/L·(cm2·d), respectively. The highest concentration of dissolved Phe released from paddy soil to overlying water due to crab bioturbation reached 80.89nullng/L, while the corresponding concentration of particulate Phe reached 267.36nullng/L. The dissolved organic carbon (DOC) and total suspended solid (TSS) concentrations in overlying water increased correspondingly and were strongly correlated with dissolved Phe and particulate Phe concentrations, respectively (P < 0.05). When 6% HA-ATP was added to the surface layer of paddy soil, the efficiency of the adsorption of Phe release was 24.00%-36.38% for particulate Phe and 89.99%-91.91% for dissolved Phe. Because HA-ATP has a large adsorption pore size (11.33 nm) and surface area (82.41nullm2/g) as well as many HA functional groups, it provided multiple hydrophobic adsorption sites for dissolved Phe, which was conducive to competitive adsorption with DOC in the overlying water. In contrast to that adsorbed by DOC, the average proportion of dissolved Phe adsorbed by HA-ATP reached 90.55%, which reduced the dissolved Phe concentration in the overlying water. Furthermore, even though the particulate Phe was resuspended by crab bioturbation, HA-ATP immobilized particulate Phe due to its capacity to inhibit desorption, which achieved the goal of reducing the Phe concentration in the overlying water. This result was confirmed by research on the adsorption-desorption characteristics of HA-ATP. This research provides an environmentally friendly in situ remediation method for reducing agricultural environmental risks and improving rice crop quality.
Subject(s)
Brachyura , Oryza , Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Animals , Polycyclic Aromatic Hydrocarbons/analysis , Soil/chemistry , Humic Substances , Ecosystem , Oryza/chemistry , Water/chemistry , Adsorption , Coculture Techniques , Adenosine Triphosphate , Soil Pollutants/analysisABSTRACT
BACKGROUND: Polycythemia vera (PV), often attributed to the JAK2 V617F mutation, is characterized by enhanced red blood cell counts in the peripheral blood. PV-associated renal disease is clinically rare; to date, there have been reports of other chronic kidney diseases related to PV, but no reports on PV-associated minimal change disease. CASE SUMMARY: A 37-year-old man presented with proteinuria and high red blood cell count on January 4, 2021. The patient underwent bone marrow and renal biopsies, then was subsequently diagnosed with PV and minimal change in disease. Hydroxyurea was administered and proteinuria remission was achieved. The patient's last visit was on April 14, 2022. CONCLUSION: We inferred that there may be a causal relationship between PV and minimal change disease.
ABSTRACT
INTRODUCTION: The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of diabetic retinopathy (DR). This study investigated the effects of circular RNA ZNF532 (circZNF532) on apoptosis and pyroptosis of RPE cells. MATERIALS AND METHODS: Blood samples were collected from patients with DR and healthy volunteers. A human RPE cell line ARPE-19 was induced by high glucose (HG) and assayed for cell viability, apoptosis, and pyroptosis. The binding of miR-20b-5p with circZNF532 and STAT3 was confirmed by a luciferase activity assay. A mouse model of diabetic retinopathy was established. RESULTS: CircZNF532 and STAT3 were upregulated but miR-20b-5p was downregulated in the serum samples of patients with DR and HG-induced ARPE-19 cells. Elevated miR-20b-5p or CircZNF532 knockdown enhanced proliferation but reduced apoptosis and pyroptosis of ARPE-19 cells. CircZNF532 sponged miR-20b-5p and inhibited its expression. STAT3 was verified as a target of miR-20b-5p. MiR-20b-5p modulated ARPE-19 cell viability, apoptosis, and pyroptosis by targeting STAT3. Mice with STZ-induced diabetes showed elevated expressions of circZNF532 and STAT3 but decreased the level of miR-20b-5p compared with the controls. Knockdown of circZNF532 inhibited apoptosis and pyroptosis in mouse retinal tissues. CONCLUSION: CircZNF532 knockdown rescued human RPE cells from HG-induced apoptosis and pyroptosis by regulating STAT3 via miR-20b-5p.
Subject(s)
Diabetic Retinopathy , MicroRNAs , RNA, Circular , Retinal Pigment Epithelium , STAT3 Transcription Factor , Animals , Apoptosis/genetics , Apoptosis/physiology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Epithelial Cells/metabolism , Glucose/metabolism , Humans , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Pyroptosis/genetics , Pyroptosis/physiology , RNA, Circular/genetics , RNA, Circular/metabolism , Retinal Pigment Epithelium/cytology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolismABSTRACT
Our previous study on the ovarian transcriptomic analysis in Leizhou black duck revealed that the ESR2 gene was involved in hormone regulation in reproduction and the estrogen signaling pathway related to reproductive performance was enriched. This suggested that ESR2 may have a functional role in the reproductive performance of the Leizhou black duck. Thus, this study aimed at evaluating the polymorphism of the ESR2 gene and its association with egg-laying traits and the distribution pattern of ESR2 mRNA in laying and non-laying Leizhou black ducks. In this study, genomic DNA was extracted from blood samples of 101 Leizhou black ducks to identify single nucleotide polymorphisms (SNPs) of the ESR2 gene to elucidate molecular markers highly associated with egg-laying traits. Four each of laying and non-laying Leizhou black ducks were selected to collect different tissues to analyze the ESR2 gene expression. A total of 23 SNPs were identified and association analysis of the single SNP sites showed that SNPs g.56805646 T>C and exon 3-20G>A were significantly (P < 0.05) associated with egg weight. Ducks with CT and AG genotypes had significantly higher (P < 0.05) egg weights than their respective other genotypes. Haplotype association analysis of g.56805646 T>C and exon 3-20G>A showed that the haplotypes were significantly associated with egg weight. Higher egg weight was seen in individuals with H3H4 haplotypes. In the hypothalamus-pituitary-gonadal (HPG) axis, the results of qRT/PCR showed that ESR2 mRNA was significantly (P < 0.05) expressed in the ovaries of both duck groups than in the hypothalamus and pituitary. In the oviduct, ESR2 was significantly (P < 0.05) higher in the infundibulum and magnum of laying and non-laying ducks respectively. This study provides a molecular marker for selecting Leizhou black ducks for egg production. In addition, it offers theoretical knowledge for studying the related biological functions of the ESR2 gene at the cellular level.
Subject(s)
Ducks , Estrogen Receptor beta , Animals , Ducks/physiology , Estrogen Receptor beta/metabolism , Gene Expression Profiling/veterinary , Reproduction/geneticsABSTRACT
BACKGROUND: Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy (HN); however, they have not been assessed in patients in the early, middle, and late phases of HN. AIM: To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease (CKD) stages 3-4 and CKD 1-2. METHODS: This study enrolled 80 patients (49 and 31 with HN at CKD stage 1-2 and 3-4, respectively) from the Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022. Plasma levels of heparan sulfate, endocan, oxidized low-density lipoprotein (Ox-LDL), E-selectin, soluble intercellular adhesion molecule-1 (slCAM1), interleukin (IL)-1ß, and IL-6 and urine levels of lipocalin-type prostaglandin D synthase (L-PGDS), IL-1ß, and IL-6 were measured using enzyme-linked immunosorbnent assay. RESULTS: Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors (P < 0.001 and P < 0.010, respectively). There were no statistical differences in sex, heart rate, body mass index, and systolic and diastolic blood pressures. The incidence of hypertension was also significant (P = 0.03). Plasma levels of heparin sulfate (P < 0.001), endocan (P = 0.034), E-selectin (P < 0.001), slCAM1 (P < 0.001), IL-1ß (P = 0.006), and IL-6 (P = 0.004) and the urine levels of L-PGDS (P < 0.001), IL-1ß (P = 0.003), and IL-6 (P < 0.001) were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2. The difference in plasma Ox-LDL levels was not significant (P = 0.078). CONCLUSION: Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2. Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.
ABSTRACT
BACKGROUND: Recent epidemiological studies have shown that general eye measurement parameters and corneal biomechanical properties can predict the speed of myopic progression in children. AIM: To investigate the correlation between the onset and progression of myopia and corneal biomechanical parameters in children. METHODS: The study included 102 cases in the emmetropia group, 207 cases in the myopic group, and 109 cases in the hyperopic group. The correlation between the change in corneal biomechanical indexes and the change in general ocular measurement parameters was analyzed. A one-way ANOVA test compared general ocular measurement and corneal biomechanical parameters. Pearson's correlation coefficient was analyzed to correlate corneal biomechanical and general ocular measurement parameters. RESULTS: The general ophthalmometric parameters: Spherical equivalent (SE), intraocular pressure (IOP), and axial length (AL), differed significantly among subjects in myopia, emmetropia, and hyperopic groups. Children's SE positively correlated with corneal biomechanical parameters: Second velocity of applanation (A2V), peak distance (PD), and deformation amplitude (DA) (P < 0.05), and second applanation length (A2L) (P < 0.05). But it was negatively correlated with PD, DA and integral radius (IR) (P < 0.05). Also, IOP was negatively correlated with A2L and IR (P < 0.05). AL positively correlated with A2V and negatively correlated with second applanation time (A2T), highest concavity, and PD. Central corneal thickness positively correlated with first applanation length, first applanation time, first applanation deformation amplitude, A2V, A2L, A2T, second applanation deformation amplitude, central curvature radius at highest concavity (HCR), PD, DA, IR, ambrosia relational thickness-horizontal, first applanation stiffness parameter, corvis biomechanical index, topographic and biomechanics index and the first velocity of applanation. The general ocular Km in children positively correlated with corneal biomechanical parameters DA and IR and negatively correlated with A2L, HCR, and PD. There was a positive correlation between the general ocular measurement parameters ΔSE and corneal biomechanical parameters ΔA2V and ΔA2L, and a negative correlation with ΔIR. The increase in general ocular measurement parameter ΔKm positively correlated with changes in corneal biomechanical parameters, ΔDA and ΔIR, and negatively correlated with ΔHCR and ΔPD. CONCLUSION: Myopia development in children was associated with multiple corneal biomechanical parameters.