Nanozymes, a groundbreaking discovery by Chinese scientists, represent a novel and remarkable property of nanomaterials. They not only exhibit catalytic activity comparable to natural enzymes, but also boast exceptional stability, tunable reactivity, and the ability to catalyze reactions under mild conditions. The identification of nanozymes has unveiled the biocatalytic potential of inorganic nanomaterials. In parallel, inorganic minerals have long been regarded as pivotal catalysts in the origin of life, driving the synthesis of early biomolecules. These minerals not only facilitate redox reactions that convert simple inorganic compounds into organic molecules but also enable chiral selection, the synthesis of biomacromolecules, and radioprotective functions via their surface structures. Recent advances suggest that inorganic nanomaterials can delicately catalyze the formation of biomolecules, aid in macromolecular assembly, and provide radiation shielding. Furthermore, nanominerals are found in abundance across Earth and extraterrestrial environments. This paper seeks to explore the potential of nanozymes as catalytic agents in the processes that gave rise to life, integrating the catalytic roles of inorganic minerals with the unique attributes of nanozymes, which will provide a new perspective for research of origin of life.

A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg·L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg·L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified.
Acetylcholinesterase ; Animals ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Ascomycota ; chemistry ; classification ; isolation & purification ; Cholinesterase Inhibitors ; isolation & purification ; metabolism ; Endophytes ; classification ; isolation & purification ; Huperzia ; microbiology ; Mice ; RAW 264.7 Cells

OBJECTIVE: To investigate the differentiation of acute promyelocytic leukemia (APL) cells induced by adenosine targeting Prx III. METHODS: HL-60 cells were divided into four groups: control group, all-trans retinoic acid (ATRA) group, adenanthin group and ATRA+adenanthin group. Cell morphologic changes were observed under optical microscope. The influence of adenanthin on the differentiation of HL-60 was observed by nitro blue tetrazolium chloride (NBT) test. Cell surface differentiation antigens CD11b expression was measured by flow cytometry. The protein expression of Prx III was detected by immunohistochemical assay. RESULTS: Adenanthin could induce the differentiation of HL-60 cells; the NBT reduction positive rate in ATRA+adenanthin group was significantly higher than that in ATRA group and adenanthin group (P＜0.05). The percentage of CD11b positive cells in ATRA+adenanthin group (43.62％±1.38％) was higher than that in adenanthin group (28.15％±1.78％), ATRA group (36.72％±1.33％) and control group (7.99％±1.78％) (P＜0. 05). The content of Prx Ⅲ protein in adenanthin group was significantly higher than that in control group and ATRA group (P＜0.05). CONCLUSION Adenanthin and ATRA have a synergistic effect on the differentiation and maturation of HL-60 cells, and its mechanism may be related with regulation of Prx III expression.
Cell Differentiation ; Diterpenes, Kaurane ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; Peroxiredoxin III ; Tretinoin

Objective Recently, the incidence of breast cancer has been the highest among female malignant tumors. Therefore, potential biomarkers are urgently needed to predict and prevent breast cancer. This study was aimed to explore the expression and clinical significance of differential miRNAs and their target genes in breast cancer by establishing miRNA expression profile in breast cancer tissues. Methods From January 2015 to December 2018, a total of 137 cases of breast cancer tissues with paired paracancerous tissues and 20 cases of breast fibroadenoma tissues were collected from the department of breast surgery, affiliated hospital of Guizhou Medical University. The tissues were divided into breast cancer group, paracancerous group, breast fibroadenoma group and lymph node metastasis group. High-throughput sequencing technique was used to detect the miRNAs in breast cancer tissues and paired paracancerous tissues. Real-time PCR verified the expressions of the three miRNAs with the most significant expression differences in different groups. Finally, bioinformatics analysis was used to predict the target genes and investigate the expression of miRNAs and proteins of target genes in different breast diseases. Results A total of 157 upregulated and 162 downregulated miRNAs were screened by high-throughput sequencing. Mir-hsa-miR-532-3p and hsa-miR-1260b were the most significant in upregulated miRNAs while has-let-7c-5p was the most significant in downregulated miRNAs. Meanwhile, bioinformatics analysis showed that their target gene was EZH2. Compared with para-cancerous group, expressions of hsa-miR-532-3p and hsa-miR-1260b were significantly upregulated while hsa-let-7c-5p was significantly down-regulated in breast cancer group and lymph node metastasis group (all P<0.05). The miRNA expressions of target gene EZH2 in breast cancer group, breast fibroadenoma group and lymph node metastasis group (1.24±0.01, 4.02±0.01, 15.97±0.01, respectively) were upregulated when compared with the para-cancerous group (1.00±0.00), and the similar conclusion could be drawn in EZH2 protein expression. Conclusion Hsa-miR-532-3p, hsa-miR-1260b and hsa-let-7c-5p were closely related to breast cancer, which may promote the occurrence and development of breast cancer by inducing the transcriptional expression of EZH2. HsamiR-532-3p, hsa-miR-1260b, hsa-let-7c-5p and EZH2 may be potential tumor biomarkers of breast cancer.

Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574^*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
Acrosome ; Adult ; China ; Codon, Nonsense ; Female ; Humans ; Male ; Membrane Proteins/genetics* ; Point Mutation ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Sequence Deletion ; Sperm Head ; Sperm Injections, Intracytoplasmic ; Teratozoospermia/genetics* ; Exome Sequencing

OBJECTIVETo explore the effect of triptolide on airway remodeling and the expression of nuclear factor-kappaB, Bcl-2 in asthmatic rats.

METHODS40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 week group; (3) Asthmatic 6 week group; (4) Therapeutic 4 week group; (5) Therapeutic 6 week group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PCNA, nuclear factor-kappaB and Bcl-2 protein were determined by immunohistochemical staining and Western blot. The expression of Bcl-2 mRNA was determined by reverse transcription-polymerase chain reaction(RT-PCR).

RESULTS(1) The expression of NF-kappaB protein in asthmatic 4 week group and asthmatic 6 week group was significantly higher than that in control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The expression of Bcl-2 protein and mRNA of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those in control group respectively (P < 0.01). The expression of Bcl-2 protein of therapeutic 6 week group was significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group respectively (P < 0.05, P < 0.01, P < 0.01), but the expression of Bcl-2 mRNA was significantly higher than the above-mentioned groups respectively (P < 0.01), the expression of Bcl-2 protein and mRNA of therapeutic 6 week group were higher than control group respectively (P < 0.05, P < 0.01). (3) The expression of PCNA protein of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of control group respectively (P < 0.01). (4) The WA/ Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01). (5) The airway resistance of asthmatic 4 week group and asthmatic 6 week group were significantly higher than those of the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 week group were significantly lower than those of asthmatic 4 week group, asthmatic 6 week group and therapeutic 4 week group, respectively (P < 0.01, P < 0.01, P < 0.05).

CONCLUSIONThe proliferation of airway smooth muscle(ASM) is related with apoptosis of airway smooth muscle cells in asthma. NF-kappaB may be involved in the process. Triptolide may prevent apoptosis of ASMCs and decrease the proliferation of ASM by inhibiting the expression of NF-kappaB, Bcl-2.

Airway Remodeling ; Animals ; Apoptosis ; Asthma ; metabolism ; pathology ; Bronchi ; cytology ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Male ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; NF-kappa B ; metabolism ; Phenanthrenes ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of curcumin on the expressions of TNF-alpha, IL-6 and IL-8 in rats with chronic nonbacterial prostatitis.

METHODSSixty healthy adult male SD rats with the body weight of 200 -220 g were equally and randomly divided into a normal control, a positive control, a model, an oral curcumin and an intraperitoneal curcumin group. The rat models of chronic nonbacterial prostatitis were made by hypodermic injection of estradiol benzoate at the dose of 0.25 mg/(kg x d) for 30 days after castration, and then treated with curcumin at 200 mg/(kg x d) by gavage or intraperitoneal injection. The positive controls received oral celebrex at 250 mg/(kg x d), while the normal control and model groups were given saline by gavage. After a week of treatment, the levels of TNF-alpha, IL-6 and IL-8 in the serum and prostate tissues of the rats were detected by ELISA assay.

RESULTSThe levels of TNF-alpha and IL-8 in the serum and prostate tissues were significantly lower in the intraperitoneal curcumin than in the positive control group (P < 0.05), but the expression of IL-6 showed no significant difference between the two groups (P > 0.01).

CONCLUSIONCurcumin is efficacious for chronic nonbacterial prostatitis in rats, and the action mechanism may be associated with its decreasing effect on the proinflammatory cytokines IL-8 and TNF-alpha in the blood and tissues.

Animals ; Chronic Disease ; Curcumin ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Phytotherapy ; Prostatitis ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVEMutation in the interleukin-7 receptor-alpha (IL-7R alpha) chain causes a rare type of severe combined immunodeficiency (SCID) with presence of NK cells in the peripheral blood. Here we report the molecular and clinical characterization of a compound heterozygosity mutation in the interleukin-7 receptor-alpha gene that resulted in SCID in a patient firstly from China.

METHODA 5 month-old male patient and his parents were enrolled in this study. Since 15 days of age, the patient had had recurrent fever, persistent cough and diarrhea. He was in poor general condition with pyorrhea and ulceration of the BCG scar. His brother died of severe infection at 4 months of age. He was initially diagnosed as SCID according to clinical manifestation and immunological analysis. A panel of SCID candidate genes including IL-2RG, RAG1/RAG2 and IL-7R alpha of patient and his parents were amplified by polymerase chain reaction (PCR) from genomic DNA. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the IL-7R alpha transcripts. Sequencing was performed directly on the PCR products forward and reversely.

RESULTThe serum immunoglobulin (Ig) profile was IgG 6867 mg/L (normal range, 3050 - 8870 mg/L); IgM 206 mg/L and IgA 249 mg/L, IgE 2.3 IU/ml (normal range < 150 IU/ml). The patient was treated with IVIG previously. There were no T-cells but increased percentage of B-cells (58%) and NK cells (42%) in the peripheral blood was found. Needle biopsies from enlarged axillary lymph node was identified positive for Mycobacterium bovis under microscope and by culture. The patient had a compound heterozygosity mutation in the IL-7R alpha gene:on one allele, there was a splice-junction mutation in intron 4 (intron 4(+1)G > A), for which his father was a carrier; whereas on the other allele, a nonsense mutation at position 638 in exon 5 with a premature stop codon (638 C > T, R206X) was identified, for which his mother was a carrier. The splice-junction mutation in intron 4 of IL-7R alpha was firstly reported. The IL-7R alpha mRNA expression of the patient was remarkably reduced whereas the parents had relatively normal IL-7R alpha mRNA expression. IL-7R alpha cDNA of the patient was amplified by nested PCR. The PCR products were purified, cloned with a TA Cloning Kit and sequenced directly. A 64 bp deletion was found in exon 4 of IL-7R alpha. No mutation was found in IL-2RG and RAG1/RAG2 of the patient and his parents.

CONCLUSIONThis is the first case with a compound heterozygosity mutation in the IL-7R receptor alpha gene and T-B+NK+ phenotype from China. Intron 4(+1)G > A was a novel mutation.

DNA ; Genome, Human ; Heterozygote ; Humans ; Infant ; Male ; Mutation ; Receptors, Interleukin-7 ; genetics ; Severe Combined Immunodeficiency ; genetics

OBJECTIVE: To explore the effect and possible mechanism of catechin microcapsulation on the repair of DNA damage in glumreular mesangial cells (GMCs) induced by H2O2. METHODS: According to H2O2 concentration, the experiment GMCs were divided into 6 groups: a control group, 50 micromol/L group, 100 micromol/L group, 150 micromol/L group, 200 micromol/L group and 250 micromol/L group. Each group was sub-divided into 3 groups: 6 h group, 12 h group and 24 h group, in order to determining the optimum dose and the best time of detecting the DNA damage in GMCs. The cultured cells were divided into 8 groups as follows: the NS control group, the H2O2 group, the catechin groups (the final concentrations were 10.0, 15.0, and 20.0 mg/L respectively) and the various catechin microcapsulation groups (the final concentrations were 10.0, 15.0, and 20.0 mg/L respectively). At the end of the experiment, hydroxy radical (OH), malonydialdehyde (MDA) and total superoxide dismutase (tSOD) concentration of supernadant in GMCs were determined by biochemistry assay, the repair of DNA damage in GMCs were detected by single cell gel electrophoresis assay. RESULTS: (1)At 6th h, H2O2 of 100 micromoL/L could cause the DNA damage of GMCs, and H2O2 of 150 micromol/L could result in DNA damage significantly. (2) No difference was found in the comet span of GMCs DNA in the catechin group and catechin microcapsulation group of different concentrations, while the DNA comet tail-long in the catechin microcapsulation group was shorter than that of the catechin group(all P(s)<0.05), and the fluorescence intensity of tail in the catechin microcapsulation group was lower than that of the catechin group(all P(s)<0.01). (3)When the concentration of catechin was 10.0 mg/L, no statistical significance was obtained in the concentration of dOH-, MDA and tSOD between the catechin microcapsulation group and the catechin group; while dOH- and MDA concentrations were lower, and the tSOD was higher in the catechin microcapsulation group than that in the catechin group when the concentration of catechin was 15.0 mg/L and 20.0 mg/L(all P(s)<0.05). CONCLUSION Catechin microcapsulation can enhance the GMCs ability of repairing DNA damage,which may be due to elevating the capacity of its anti-oxidation by catechin microcapsulation.
Animals ; Capsules ; Catechin ; pharmacology ; Cells, Cultured ; Comet Assay ; DNA Damage ; drug effects ; DNA Repair ; drug effects ; Dose-Response Relationship, Drug ; Hydrogen Peroxide ; toxicity ; Hydroxyl Radical ; metabolism ; Malondialdehyde ; metabolism ; Mesangial Cells ; drug effects ; metabolism ; pathology ; Rats ; Superoxide Dismutase ; metabolism

OBJECTIVE: To investigate the eliminating ability of catechin to eliminate O2-* and *OH. METHODS: The ability of catechin to clear away O2-* and *OH was respectively measured by faintness chemiluminescence and spin trapping assay. RESULTS: IC50 that catechin eliminated O2-* and *OH was 6.16, 0.59 g/mL respectively, and the eliminating ability of catechin was much stronger than that of the extract from liquorice, rosemary, grape pip, giant knotweed and ginkgo leaf. CONCLUSION Compared with several important natural plants of antioxidants, the eliminating ability of cathechin is the best.
Antioxidants ; pharmacology ; Catechin ; pharmacology ; Free Radical Scavengers ; pharmacology ; Hydroxyl Radical ; metabolism ; Luminescent Measurements ; Superoxides ; metabolism