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1.
Sci Total Environ ; 946: 173907, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38906294

ABSTRACT

The worldwide dissemination of New Delhi metallo-ß-lactamase-1 (NDM-1), which mediates resistance to almost all clinical ß-lactam antibiotics, is a major public health problem. The global distribution, species, sources, and potential transfer risk of blaNDM-1-carrying bacteria are unclear. Results of a comprehensive analysis of literature in 2010-2022 showed that a total of 6002 blaNDM-1 carrying bacteria were widely distributed around 62 countries with a high trend in the coastal areas. Opportunistic pathogens or pathogens like Klebsiella sp., Escherichia sp., Acinetobacter sp. and Pseudomonas sp. were the four main species indicating the potential microbial risk. Source analysis showed that 86.45 % of target bacteria were isolated from the source of hospital (e.g., Hospital patients and wastewater) and little from surface water (5.07 %) and farms (3.98 %). A plasmid-encoded blaNDM-1Acinetobacter sp. with the resistance mechanisms of antibiotic efflux pump, antibiotic target change and antibiotic degradation was isolated from the wastewater of a typical tertiary hospital. Insertion sequences (IS3 and IS30) located in the adjacent 5 kbp of blaNDM-1-bleMBL gene cluster indicating the transposon-mediated horizontal gene transfer risk. These results showed that the worldwide spread of blaNDM-1-carrying bacteria and its potential horizontal gene transfer risk deserve good control.

3.
Int J Parasitol Drugs Drug Resist ; 25: 100539, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38621317

ABSTRACT

Infection with Plasmodium falciparum is often deadly when it results in cerebral malaria, which is associated with neuropathology described as an overwhelming inflammatory response and mechanical obstruction of cerebral microvascular. PI3Kγ is a critical component of intracellular signal transduction and plays a central role in regulating cell chemotaxis, migration, and activation. The purpose of this study was to examine the relationship between inhibiting the PI3Kγ pathway and the outcome of experimental cerebral malaria (ECM) in C57BL/6J mice infected with the mouse malaria parasite, Plasmodium berghei ANKA. We observed that oral administration of the PI3Kγ inhibitor IPI549 after infection completely protected mice from ECM. IPI549 treatment significantly dampened the magnitude of inflammatory responses, with reduced production of pro-inflammatory factors, decreased T cell activation, and altered differentiation of antigen-presenting cells. IPI549 treatment protected the infected mice from neuropathology, as assessed by an observed reduction of pathogenic T cells in the brain. Treating the infected mice with IPI549 three days after parasite inoculation improved the murine blood brain barrier (BBB) integrity and helped the mice pass the onset of ECM. Together, these data indicate that oral administration of the PI3Kγ inhibitor IPI549 has a suppressive role in host inflammation and alleviates cerebral pathology, which supports IPI549 as a new malaria treatment option with potential therapeutic implications for cerebral malaria.

4.
Small ; : e2400919, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639010

ABSTRACT

Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.

5.
Int Immunopharmacol ; 131: 111817, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38460299

ABSTRACT

Adjuvants are critical components for vaccines, which enhance the strength and longevity of the antibody response and influence the types of immune response. Limited research has been conducted on the immunogenicity and protective efficacy of various adjuvants in malaria transmission-blocking vaccines (TBVs). In this study, we formulated a promising TBV candidate antigen, the P. berghei ookinete surface antigen PSOP25, with different types of adjuvants, including the TLR4 agonist monophosphoryl lipid A (MPLA), the TLR9 agonist cytosine phosphoguanosine oligodeoxynucleotides (CpG ODN 1826) (CpG), a saponin adjuvant QS-21, aluminum hydroxide (Alum), and two combination adjuvants MPLA + QS-21 and QS-21 + CpG. We demonstrated that adjuvanted vaccines results in elevated elicited antibody levels, increased proliferation of plasma cells, and efficient formation of germinal centers (GCs), leading to enhanced long-term protective immune responses. Furthermore, CpG group exhibited the most potent inhibition of ookinete formation and transmission-blocking activity. We found that the rPSOP25 with CpG adjuvant was more effective than MPLA, QS-21, MPLA + QS-21, QS-21 + CpG adjuvants in dendritic cells (DCs) activation and differentiation. Additionally, the CpG adjuvant elicited more rubust immune memory response than Alum adjuvant. CpG and QS-21 adjuvants could activate the Th1 response and promote the secretion of IFN-γ and TNF-α. PSOP25 induced a higher number of Tfh cells in splenocytes when combined with MPLA, CpG, and QS-21 + CpG; and there was no increase in these cell populations when PSOP25 was administered with Alum. In conclusion, CpG may confer enhanced efficacy for the rPSOP25 vaccine, as evidenced by the ability of the elicited antisera to induce protective immune responses and improved transmission-blocking activity.


Subject(s)
Malaria Vaccines , Malaria , Humans , Adjuvants, Immunologic , Alum Compounds , Aluminum Hydroxide , Malaria/prevention & control , Oligodeoxyribonucleotides
6.
Acta Biomater ; 173: 482-494, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37981044

ABSTRACT

Acute kidney injury (AKI) is a prevalent condition in critically ill patients that is often associated with significant morbidity and mortality. As the lack of effective early diagnosis methods often delays AKI treatment, there is currently no definitive clinical intervention available. In this study, we aimed to address these challenges by developing a nano-system called Platelet membranes-ICG-SS31-PLGA (PISP), which was designed to selectively target to the kidney site, taking advantage of the natural tendency of platelets to accumulate at sites of vascular injury. This approach allowed for the accumulation of PISP within the kidney as the disease progresses. By incorporating ICG, the in vivo distribution of PISP can be observed for NIR diagnosis of AKI. This non-invasive imaging technique holds great promise for early detection and monitoring of AKI. Furthermore, Elamipretide (SS31) acts as a mitochondria-targeted antioxidant that protects against mitochondrial damage and reduces oxidative stress, inflammation, and apoptosis. The combination of diagnostic and therapeutic capabilities within a single nano-system makes the PISP approach a valuable tool for addressing AKI. This intervention helps to prevent the deterioration of AKI and promotes the recovery. STATEMENT OF SIGNIFICANCE.


Subject(s)
Acute Kidney Injury , Nanoparticles , Humans , Antioxidants/pharmacology , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Acute Kidney Injury/diagnosis , Acute Kidney Injury/drug therapy , Kidney , Nanoparticles/therapeutic use
7.
J Mater Chem B ; 11(38): 9185-9200, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37724440

ABSTRACT

Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting ability severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) is developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (˙OH), exerting an assisted chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S), leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.


Subject(s)
Colonic Neoplasms , Nanospheres , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Iodides , Phototherapy/methods , Cobalt/pharmacology , Colonic Neoplasms/drug therapy , Hydroxides
8.
Front Immunol ; 14: 1135657, 2023.
Article in English | MEDLINE | ID: mdl-36969161

ABSTRACT

Background: The immune microenvironment is of great significance in cervical cancer. However, there is still a lack of systematic research on the immune infiltration environment of cervical cancer. Methods: We obtained cervical cancer transcriptome data and clinical information from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, evaluated the immune microenvironment of cervical cancer, determined immune subsets, constructed an immune cell infiltration scoring system, screened key immune-related genes, and performed single-cell data analysis and cell function analysis of key genes. Results: We combined the TCGA and GEO data sets and obtained three different immune cell populations. We obtained two gene clusters, extracted 119 differential genes, and established an immune cell infiltration (ICI) scoring system. Finally, three key genes, IL1B, CST7, and ITGA5, were identified, and single-cell sequencing data were mined to distribute these key genes in different cell types. By up-regulating CST7 and down-regulating IL1B and ITGA5, cervical cancer cells' proliferation ability and invasion ability were successfully reduced. Conclusion: We conducted a comprehensive assessment of the state of the tumor immune microenvironment in cervical cancer, constructed the ICI scoring system, and identified the ICI scoring system as a potential indicator of susceptibility to immunotherapy for cervical cancer, identifying key genes suggesting that IL1B, CST7, and ITGA5 play an essential role in cervical cancer.


Subject(s)
Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/therapy , Immunotherapy , Prognosis , Multigene Family , Cell Proliferation , Tumor Microenvironment/genetics
9.
Front Surg ; 10: 1110040, 2023.
Article in English | MEDLINE | ID: mdl-36969760

ABSTRACT

Background: The tumor biology of neuroendocrine prostate cancer (NEPC) is different from that of ordinary prostate cancer, herefore, existing clinical prognosis models for prostate cancer patients are unsuitable for NEPC. The specialized individual situation assessment and clinical decision-making tools for NEPC patients are urgently needed. This study aimed to develop a valid NEPC prognostic nomogram and risk stratification model to predict risk associated with patient outcomes. Methods: We collected 340 de-novo NEPC patients from the SEER database, and randomly selected 240 of them as the training set and the remaining 100 as the validation set. Cox regression model was used to screen for risk factors affecting overall survival (OS) and cancer-specific survival (CSS) and construct a corresponding nomogram. The receiver operating characteristic (ROC) curves, calibration curves, C-indexes, and decision curve analysis (DCA) curves are used to verify and calibrate nomograms. Results: NEPC prognosis nomograms were constructed by integrating independent risk factors. The C-indexes, ROC curves, calibration curves, and DCA curves revealed excellent prediction accuracy of the prognostic nomogram. Furthermore, we demonstrated that NEPC patients in the high-risk group had significantly lower OS and CSS than those in the low-risk group with risk scores calculated from nomograms. Conclusions: The nomogram established in this research has the potential to be applied to the clinic to evaluate the prognosis of NEPC patients and support corresponding clinical decision-making.

10.
Arch Med Sci ; 19(1): 160-170, 2023.
Article in English | MEDLINE | ID: mdl-36817666

ABSTRACT

Introduction: To explore the function of interleukin 1α (IL-1α) in bladder cancer (BCa). Material and methods: Immunohistochemistry (IHC) was used to test the protein expression of IL-1α in BCa tissues. The relationship between IL-1α and clinical characteristics was analyzed by the Kaplan-Meier curve method. The gene and protein expression was tested by reverse transcription quantitative polymerase chain reaction (RT-q-PCR) and western blot, respectively. Colony formation and MTT assays were used to detect the potential of proliferation in vitro, and scratch and transwell chamber assays were used to detect the potential of invasion in vitro. Markers of proliferation such as Ki-67 and proliferating cell nuclear antigen (PCNA) and markers of invasion such as MMP-2 and MMP-9 were detected by western blot. Xenograft study was used for the in vivo experiment. Results: We found that IL-1α was highly expressed in BCa patients while highly expressed IL-1α was significantly related to short overall survival and progression-free survival in BCa as well. Moreover, knockdown of IL-1α might inhibit the ability of cancer cells to proliferate and invade or migrate both in vitro and in vivo. Conclusions: Our findings suggested that IL-1α might be a therapy target for BCa malignant progression.

11.
Colloids Surf B Biointerfaces ; 222: 113117, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36586238

ABSTRACT

Photodynamic therapy (PDT) has many exceptional advantages in cancer treatment, such as minor trauma, low toxicity side effects, and strong adaptability, effectively overcoming some obstacles of traditional therapy and providing more revolutionary opportunities for curing cancer. Chlorin e6 (Ce6) exhibits excellent singlet oxygen generation and conversion efficiency under near-infrared laser irradiation and is a promising PDT photosensitizer. However, its hydrophobicity, short half-life and lack of tumor specificity limit its in vivo anticancer application. Therefore, this work has designed and prepared a multifunctional nanoplatform, Ce6/FeOOH@BSA, to efficiently deliver Ce6. Nanoparticles exhibit excellent dispersion and stability in deionized water, PBS and DMEM, and the blood half-life is 3.98 ± 0.31 h. The nanoplatform demonstrates effective tumor targeting and accumulation, overcoming the obstacles of the biological application of Ce6. Iron ions can exert a chemodynamic therapy (CDT) effect by reacting with overexpressed H2O2 in the tumor to generate toxic hydroxyl radicals (·OH). Moreover, FeOOH nanoparticles effectively promote glutathione (GSH) consumption in tumor cells, which is conducive to accumulating reactive oxygen species (ROS). In brief, Ce6/FeOOH@BSA nanoparticles realize the targeted delivery of Ce6 and mediate synergistic PDT/CDT against tumors, broadening the biomedical application of nanomaterials.


Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Porphyrins , Humans , Photosensitizing Agents/pharmacology , Hydrogen Peroxide , Neoplasms/drug therapy , Cell Line, Tumor , Porphyrins/pharmacology
12.
Technol Cancer Res Treat ; 21: 15330338221104565, 2022.
Article in English | MEDLINE | ID: mdl-35929135

ABSTRACT

Background: Epithelial ovarian cancer (EOC) remains the leading cause of gynecologic cancer death worldwide due to the high recurrence rate. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality for platinum-sensitive recurrent EOC. The latest studies demonstrate homologous recombination-related (HRR) mutation status increases the sensitivity to platinum-based chemotherapy drugs in EOC. However, the molecular analysis of recurrent EOC patient benefits from HIPEC is unknown. Thus, we aimed to evaluate the efficacy and safety of CRS combined with HIPEC for platinum-sensitive in recurrent EOC with HRR mutation. Methods: This is a phase III randomized controlled clinical trial in patients with platinum-sensitive recurrent EOC. Participants were divided into 2 groups based on the HRR mutation status and randomized to receive CRS + HIPEC. The patients then received periodic chemotherapy and follow-up. Results: The primary objective of this study was to evaluate the effect of CRS + HIPEC compared to CRS alone in patients with a platinum-sensitive recurrent EOC stratified for HRD status. We hypothesize that the addition of HIPEC to CRS improves the progression-free survival (PFS) of platinum-sensitive recurrent EOC patients with HRR mutation compared with patients without HRR mutation. Conclusion: Recurrent EOC has a poor prognosis due to implantation and metastasis in the abdominal cavity. Intraperitoneal chemotherapy reduced seeding by removing free tumor cells. HIPEC utilizes physical and biological properties to significantly increase the clearance rate of tumors. Van Driel WJ et al proposed that HIPEC using platinum-based chemotherapy improves the survival of patients with ovarian cancer. HRR mutation, as a common pathogenic mutation in ovarian cancer, has a predictive effect on the platinum sensitivity of ovarian cancer patients. Whether lobaplatin-based HIPEC will play a greater role in ovarian cancer patients with HRR mutations is currently unknown.


Subject(s)
Antineoplastic Agents , Hyperthermia, Induced , Ovarian Neoplasms , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Female , Homologous Recombination , Humans , Hyperthermic Intraperitoneal Chemotherapy , Mutation , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Platinum , Survival Rate
13.
J Hazard Mater ; 439: 129549, 2022 10 05.
Article in English | MEDLINE | ID: mdl-35868090

ABSTRACT

The excessive dissemination of New Delhi metallo-ß-lactamase-1 (NDM-1), which mediates resistance to a majority of clinical ß-lactam antibiotics, has created a major public health problem worldwide. Herein, a blaNDM-1-carrying (plasmid encoded) super-resistant bacterium, Acinetobacter sp. CS-2, was selected to reveal its mechanisms of inactivation and photoreactivation during UV, chlorination and UV/chlorination disinfection. The inactivated CS-2 underwent a certain photoreactivation after UV and chlorination. The logistic model precisely fitted the data obtained in the photoreactivation experiments by UV treatment, with the estimated kinetic parameters Sm (0.530%-12.071%) and k2 (0.0009-0.0471). The photoreactivation of Acinetobacter sp. CS-2 was observed when treated by chlorination at a dosage of 0.5 mg/L with a survival ratio of 34.04%. UV/chlorination not only resulted in the high-efficiency reduction of CS-2 but also effectively controlled its photoreactivation with a survival ratio of 0%- 0.87%. UV/chlorination showed great advantages in causing the irreversible destruction of bacterial surface structures by making the cell membranes wrinkled and incomplete compared with UV disinfection. The singlet oxygen (1O2) generated during UV/chlorination treatment played a vital role in blaNDM-1 removal. This study proposed new insights into the mechanism of inactivation and the characteristics of photoreactivation for the super-resistant bacteria by UV, chlorination and UV/chlorination.


Subject(s)
Halogenation , Ultraviolet Rays , Anti-Bacterial Agents , Bacteria , Disinfection/methods , beta-Lactamases
14.
Front Oncol ; 12: 840363, 2022.
Article in English | MEDLINE | ID: mdl-35444945

ABSTRACT

Purpose: To assess the impact of enhanced recovery after surgery (ERAS) protocols in laparoscopic radical nephrectomy (LRN). Methods: The clinical data of 89 patients underwent LRN in Zhongnan Hospital of Wuhan University from February 2019 to September 2021 were collected (40 in the ERAS group and 49 in the pre-ERAS group). The clinical characteristics, prognosis, and length of hospital stay (LOS) were compared between the two groups using t test, Mann-Whitney test, and chi-square test. Results: Total LOS and postoperative LOS were significantly shorter in ERAS group than in pre-ERAS group [15.0 (13.5-19.5) vs. 12.0 (10.0-14.0), P < 0.001; 8.0 (7.0-10.0) vs. 7.0 (5.0-8.8), P = 0.001]. Compared with the pre-ERAS group, the hospitalization expenses of the ERAS group were also lower (P = 0.023). In addition, the incidence of postoperative complications in the ERAS group also decreased (P = 0.054). Conclusions: ERAS protocol in LRN could help accelerate the recovery of patients and is worthy of clinical promotion.

15.
Microbiol Spectr ; 10(2): e0015022, 2022 04 27.
Article in English | MEDLINE | ID: mdl-35404079

ABSTRACT

Gametogenesis is essential for malaria parasite transmission, but the molecular mechanism of this process remains to be refined. Here, we identified a G-protein-coupled receptor 180 (GPR180) that plays a critical role in signal transduction during gametogenesis in Plasmodium. The P. berghei GPR180 was predominantly expressed in gametocytes and ookinetes and associated with the plasma membrane in female gametes and ookinetes. Knockout of pbgpr180 (Δpbgpr180) had no noticeable effect on blood-stage development but impaired gamete formation and reduced transmission of the parasites to mosquitoes. Transcriptome analysis revealed that a large proportion of the dysregulated genes in the Δpbgpr180 gametocytes had assigned functions in cyclic nucleotide signal transduction. In the Δpbgpr180 gametocytes, the intracellular cGMP level was significantly reduced, and the cytosolic Ca2+ mobilization showed a delay and a reduction in the magnitude during gametocyte activation. These results suggest that PbGPR180 functions upstream of the cGMP-protein kinase G-Ca2+ signaling pathway. In line with this functional prediction, the PbGPR180 protein was found to interact with several transmembrane transporter proteins and the small GTPase Rab6 in activated gametocytes. Allele replacement of pbgpr180 with the P. vivax ortholog pvgpr180 showed equal competence of the transgenic parasite in sexual development, suggesting functional conservation of this gene in Plasmodium spp. Furthermore, an anti-PbGPR180 monoclonal antibody and the anti-PvGPR180 serum possessed robust transmission-blocking activities. These results indicate that GPR180 is involved in signal transduction during gametogenesis in malaria parasites and is a promising target for blocking parasite transmission. IMPORTANCE Environmental changes from humans to mosquitoes activate gametogenesis of the malaria parasite, an obligative process for parasite transmission, but how the signals are relayed remains poorly understood. Here, we show the identification of a Plasmodium G-protein-coupled receptor, GPR180, and the characterization of its function in gametogenesis. In P. berghei, GPR180 is dispensable for asexual development and gametocytogenesis, but its deletion impairs gametogenesis and reduces transmission to mosquitoes. GPR180 appears to function upstream of the cGMP-protein kinase G-Ca2+ signaling pathway and is required for the maximum activity of this pathway. Genetic complementation shows that the GPR180 ortholog from the human malaria parasite P. vivax was fully functional in P. berghei, indicating functional conservation of GPR180 in Plasmodium spp. With predominant expression and membrane association of GPR180 in sexual stages, GPR180 is a promising target for blocking transmission, and antibodies against GPR180 possess robust transmission-blocking activities.


Subject(s)
Culicidae , Malaria , Parasites , Animals , Cyclic GMP-Dependent Protein Kinases/genetics , Cyclic GMP-Dependent Protein Kinases/metabolism , Female , Gametogenesis/genetics , Humans , Malaria/parasitology , Plasmodium berghei/genetics , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction
16.
Sheng Wu Gong Cheng Xue Bao ; 38(2): 546-564, 2022 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-35234381

ABSTRACT

Ribosomal engineering is a technique that can improve the biosynthesis of secondary metabolites in the antibiotics-resistant mutants by attacking the bacterial RNA polymerase or ribosome units using the corresponding antibiotics. Ribosomal engineering can be used to discover and increase the production of valuable bioactive secondary metabolites from almost all actinomycetes strains regardless of their genetic accessibility. As a consequence, ribosomal engineering has been widely applied to genome mining and production optimization of secondary metabolites in actinomycetes. To date, more than a dozen of new molecules were discovered and production of approximately 30 secondary metabolites were enhanced using actinomycetes mutant strains generated by ribosomal engineering. This review summarized the mechanism, development, and protocol of ribosomal engineering, highlighting the application of ribosomal engineering in actinomycetes, with the aim to facilitate future development of ribosomal engineering and discovery of actinomycetes secondary metabolites.


Subject(s)
Actinobacteria , Actinobacteria/genetics , Actinobacteria/metabolism , Actinomyces/genetics , Anti-Bacterial Agents/metabolism , Multigene Family , Ribosomes/genetics
17.
Technol Cancer Res Treat ; 21: 15330338211067911, 2022.
Article in English | MEDLINE | ID: mdl-35343831

ABSTRACT

Background: Increasing evidences have shown that abnormal alternative splicing (AS) events are closely related to the prognosis of various tumors. However, the role of AS in ovarian cancer (OV) is poorly understood. This study aims to explore the correlation between AS and the prognosis of OV and establish a prognostic model for OV. Methods: We downloaded the RNA-seq data of OV from The Cancer Genome Atlas databases and assessed cancer-specific AS through the SpliceSeq software. Then systemically investigated the overall survival (OS)-related AS and splicing factors (SFs) by bioinformatics analysis. The nomogram was established based on the clinical information, and the clinical practicability of the nomogram was verified through the calibration curve. Finally, a splicing correlation network was constructed to reveal the relationship between OS-related AS and SFs. Results: A total of 48,049 AS events were detected from 10,582 genes, of which 1523 were significantly associated with OS. The area under the curve of the final prediction model was 0.785, 0.681, and 0.781 in 1, 3, and 5 years, respectively. Moreover, the nomogram showed high calibration and discrimination in OV patients. Spearman correlation analysis was used to determine 8 SFs significantly related to survival, including major facilitator superfamily domain containing 11, synaptotagmin binding cytoplasmic RNA interacting protein, DEAH-box helicase 35, CWC15, integrator complex subunit 1, LUC7 like 2, cell cycle and apoptosis regulator 1, and heterogeneous nuclear ribonucleoprotein A2/B1. Conclusion: This study provides a prognostic model related to AS in OV, and constructs an AS-clinicopathological nomogram, which provides the possibility to predict the long-term prognosis of OV patients. We have explored the wealth of RNA splicing networks and regulation patterns related to the prognosis of OV, which provides a large number of biomarkers and potential targets for the treatment of OV. Put forward the potential possibility of interfering with the AS of OV in the comprehensive treatment of OV.


Subject(s)
Alternative Splicing , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial/genetics , Gene Expression Regulation, Neoplastic , Humans , Ovarian Neoplasms/genetics , Prognosis
18.
J Hazard Mater ; 430: 127414, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35149504

ABSTRACT

Antibiotic resistance genes (ARGs) and their host antibiotic-resistant bacteria (ARB) are widely detected in the environment and pose a threat to human health. Traditional disinfection in water treatment plants cannot effectively remove ARGs and ARB. This study explored the potential of a heterogeneous photo-Fenton-like process utilizing a hierarchical macro-mesoporous Co3O4-SiO2 (MM CS) catalyst for activation of peroxymonosulfate (PMS) to inactivate ARB and degrade the intracellular ARGs. A typical gram-negative antibiotic-resistant bacteria called Pseudomonas sp. HLS-6 was used as a model ARB. A completed inactivation of ARB at ∼107 CFU/mL was achieved in 30 s, and an efficient removal rate of more than 4.0 log for specific ARGs (sul1 and intI1) was achieved within 60 min by the MM CS-based heterogeneous photo-Fenton-like process under visible light and neutral pH conditions. Mechanism investigation revealed that •O2- and 1O2 were the vital reactive species for ARB inactivation and ARG degradation. The formation and transformation of the active species were proposed. Furthermore, the hierarchical macro-mesoporous structure of MM CS provided excellent optical and photoelectrochemical properties that promoted the cycle of Co3+/Co2+ and the effective utilization of PMS. This process was validated to be effective in various water matrices, including deionized water, underground water, source water, and secondary effluent wastewater. Collectively, this work demonstrated that the MM CS-based heterogeneous photo-Fenton-like process is a promising technology for controlling the spread of antibiotic resistance in aquatic environments.


Subject(s)
Angiotensin Receptor Antagonists , Silicon Dioxide , Angiotensin-Converting Enzyme Inhibitors , Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Cobalt , Drug Resistance, Microbial/genetics , Genes, Bacterial , Humans , Oxides , Peroxides , Wastewater
19.
Chemosphere ; 291(Pt 2): 132837, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34762889

ABSTRACT

Various pollutants are released during pharmaceutical production processes, which is of great concern. Most studies have focused on the terminal treatment results of mixed pharmaceutical wastewater, and further research on wastewater from the production processes is required. This study investigated the wastewater quality indicators, residual antibiotics, and biological toxicity of the wastewater during the production process in a large pharmaceutical producing factory in Northern China. The wastewater contained numerous organic pollutants, with the chemical oxygen demand (COD) values ranging from 2.0 × 103 to 2.6 × 105 mg L-1 and the total nitrogen (TN) values ranging from 1.3 × 103 to 2.0 × 104 mg L-1. High concentrations of cephalexin and cefradine remained in the wastewater of the production workshop, with the highest concentration of cefradine reaching 1328 mg L-1. The wastewater from the oxidation and solvent recovery workshops was more toxic to Vibrio fischeri and Daphnia magna than that of other workshops. Moreover, the biological acute toxicity of wastewater was significantly correlated with the concentration of COD and TN (p < 0.01). This study provides new insights into the treatment of antibiotic production wastewater, illuminating the incomplete extraction of products and the significant risk posed by pharmaceutical wastewater to the environment.


Subject(s)
Pharmaceutical Preparations , Water Pollutants, Chemical , Aliivibrio fischeri , Animals , Anti-Bacterial Agents/toxicity , Daphnia , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
20.
World J Clin Cases ; 9(26): 7850-7856, 2021 Sep 16.
Article in English | MEDLINE | ID: mdl-34621837

ABSTRACT

BACKGROUND: Primary omental tumors are uncommon, and omental fibromas account for 2% of these tumors. Due to the low incidence of omental fibromas and the limited relevant literature, it is challenging for clinicians to make an accurate diagnosis of this condition, especially before surgery. CASE SUMMARY: A 30-year-old man was admitted to the hospital because of a left epididymal mass with vague discomfort for more than 1 mo. A physical examination was performed, and the findings showed that the epididymal mass may have entered the abdominal cavity. Pelvic computed tomography was performed in our hospital and revealed a left inguinal hernia with a mass in the hernial contents, and no masses were found in the left epididymis. A traditional inguinal hernia incision was made. Intraoperative hernia contents were found to be of the greater omentum, and a 2.5 cm-diameter mass was found at the distal end of the greater omentum. The scrotum and epididymis did not exhibit other masses. Then, the mass of the greater omentum was excised. Intraoperative frozen pathological examination suggested a spindle cell tumor. The postoperative pathological examination suggested that the mass was an omental angiofibroma. Postoperatively, the patient recovered well and was discharged. Outpatient re-examinations were performed at 1 mo and half a year after the operation and showed no obvious abnormalities. CONCLUSION: Due to the low morbidity rate associated with and latent nature of omental tumors, these tumors are difficult to diagnose preoperatively; thorough medical history taking, detailed physical examinations, and necessary imaging auxiliary examinations can help clinicians diagnose and treat these cases.

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