ABSTRACT
Class IIa bacteriocins produced in lactic acid bacteria are short cationic peptides with antimicrobial activity. In the search for new biopreservation agents, class IIa bacteriocins are considered to be the best potential candidates, not only due to their large abundance but also because of their high biological activity and excellent thermal stability. However, regulated by the biosynthetic regulatory system, the natural class IIa bacteriocin yield is low, and the extraction process is complicated. The biotechnological production of class IIa bacteriocins in various cell factories has been attempted to improve this situation. In this review, we focus on the application of biotechnological routes for class IIa bacteriocin production. The drawbacks and improvements in the production of class IIa bacteriocins in various cell factories are discussed. Furthermore, we present the main challenge of class IIa bacteriocins, focusing on increasing their production by constructing suitable cell factories. Recombinant bacteriocins have made considerable progress from inclusion body formation, dissolved form and low antibacterial activity to yield recovery. The development of prospective cell factories for the biotechnological production of bacteriocins is still required, which may facilitate the application of bacteriocins in the food industry.
Subject(s)
Bacteriocins , Biotechnology , Bacteriocins/biosynthesis , Biotechnology/methods , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/pharmacology , Recombinant Proteins/metabolism , Recombinant Proteins/biosynthesis , Lactobacillales/metabolismABSTRACT
By extracting the acupoint names and their main indications from cases in Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion, the acupoints and their main indications are represented in a reduced dimension, establishing an "acupoint-indication" linkage. Using complex network detection results (node degree values), the specificity of acupoints was assessed. The small-world characteristics of the "acupoint-indication" network are utilized to analyze the consistency of acupoint selection in acupuncture prescriptions and strategies to avoid redundant acupoints. The results show that the "acupoint-indication" network formed by both texts exhibited an approximate "long-tail" distribution, with a large number of node degree values concentrated between 0 and 4 000, while a few nodes have degree values exceeding 10 000. There are significant differences in the number and distribution of nodes with degree values> 10 000 between the two texts. Chinese Acupuncture and Moxibustion Therapy includes 11 acupoints with multiple edges across the body, whereas Practical Acupuncture and Moxibustion contains only 2 such acupoints, located in the lower limbs. Clinically, some acupoints have a broad therapeutic effect and appear in numerous prescriptions. The division of acupoints based on node degree values can coarsely evaluate the body region specificity of acupoints' regulatory effects. The "acupoint-indication" network of Chinese Acupuncture and Moxibustion Therapy has a higher number of edges than that of Practical Acupuncture and Moxibustion, which might be related to the different historical contexts of the two texts. In the future, diagnostic and therapeutic patterns with historical continuity can be utilized to optimize acupuncture prescriptions.
Subject(s)
Acupuncture Points , Acupuncture Therapy , Moxibustion , Humans , China , Moxibustion/methods , Textbooks as TopicABSTRACT
Tumor immunotherapy is a promising approach for addressing the limitations of conventional tumor treatments, such as chemotherapy and radiotherapy, which often have side effects and fail to prevent recurrence and metastasis. However, the effectiveness and sustainability of immune activation in tumor immunotherapy remain challenging. Tumor immunogenic cell death, characterized by the release of immunogenic substances, damage associated molecular patterns (DAMPs), and tumor associated antigens, from dying tumor cells (DTCs), offers a potential solution. By enhancing the immunogenicity of DTCs through the inclusion of more immunogenic antigens and stimulating factors, immunogenic cell death (ICD) based cancer vaccines can be developed as a powerful tool for immunotherapy. Integrating ICD nanoinducers into conventional treatments like chemotherapy, photodynamic therapy, photothermal therapy, sonodynamic therapy, and radiotherapy presents a novel strategy to enhance treatment efficacy and potentially improve patient outcomes. Preclinical research has identified numerous potential ICD inducers. However, effectively translating these findings into clinically relevant applications remains a critical challenge. This review aims to contribute to this endeavor by providing valuable insights into the in vitro preparation of ICD-based cancer vaccines. We explored established tools for ICD induction, followed by an exploration of personalized ICD induction strategies and vaccine designs. By sharing this knowledge, we hope to stimulate further development and advancement in the field of ICD-based cancer vaccines.
Subject(s)
Cancer Vaccines , Immunogenic Cell Death , Neoplasms , Humans , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Immunogenic Cell Death/drug effects , Neoplasms/immunology , Neoplasms/therapy , Animals , Immunotherapy/methods , Antigens, Neoplasm/immunologyABSTRACT
Transplantation of bone marrow mesenchymal stem cells (BMSCs) has demonstrated promising clinical utility in the treatment of endometrial injury and the restoration of fertility. However, since the efficacy of BMSCs after transplantation is not stable, it is very important to find effective ways to enhance the utilisation of BMSCs. Electroacupuncture (EA) has some positive effects on the chemotaxis of stem cells and diseases related to uterine injury. In this study, we established the intrauterine adhesion (IUA) model of the Sprague-Dawley rat using lipopolysaccharide infection and mechanical scratching. Phosphate-buffered saline, BMSCs alone, and BMSCs combined with EA were randomly administered to the rats. Fluorescent cell labelling showed the migration of transplanted BMSCs. H&E staining, Masson staining, Western blot, immunohistochemistry, ELISA, and qRT-PCR were utilised to detect changes in endometrial morphology and expressions of endometrial receptivity-related factors, endometrial pro-inflammatory factors, and fibrosis factors. Finally, we conducted a fertility test to measure the recovery of uterine function. The results showed that EA promoted transplanted BMSCs to migrate into the injured uterus by activating the SDF-1/CXCR4 axis. Endometrial morphology showed the most significant improvement in the BMSC + EA group. The expressions of endometrial pro-inflammatory factors and fibrosis indexes in the BMSC + EA group were lower than those in the model and BMSC groups. Further studies revealed that the expression of endometrial receptivity-related factors and the number of embryos implanted on day 8 of gestation increased in the BMSC + EA group compared with the model group and the BMSC group.
Subject(s)
Electroacupuncture , Mesenchymal Stem Cell Transplantation , Rats, Sprague-Dawley , Uterine Diseases , Animals , Female , Electroacupuncture/methods , Mesenchymal Stem Cell Transplantation/methods , Tissue Adhesions , Rats , Uterine Diseases/therapy , Uterine Diseases/pathology , Endometrium/metabolism , Combined Modality Therapy , Recovery of Function , Uterus , Mesenchymal Stem Cells , Receptors, CXCR4/metabolism , Chemokine CXCL12/metabolism , Disease Models, AnimalABSTRACT
OBJECTIVES: Hemoglobin (Hb) Lepore and Hb anti-Lepore are infrequent fusion gene variants that result from nonhomologous crossovers during meiosis. Conventional molecular testing methods may face challenges in identifying these variants. During Hb analysis using capillary electrophoresis, we encountered 6 cases with unusual Hb variants. Our aim was to identify the alterations in their globin genes. METHODS: Gap-polymerase chain reaction (PCR), reverse dot-blot assay (RDB), Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-read single-molecule real-time (SMRT) sequencing were used to confirm the presence of globin gene alterations. RESULTS: The routine thalassemia gene test kit using the gap-PCR and RDB techniques did not detect common gene variations. Direct sequencing failed to identify any known or unknown globin gene alterations. The MLPA analysis, however, revealed the possible presence of α-globin gene triplications as well as 2 types of fusion gene alterations. Further analysis using long-read SMRT sequencing accurately identified 3 rare gene variations: αααanti-3.7, Hb Lepore-Boston-Washington, and Hb anti-Lepore P-India. CONCLUSIONS: Conventional methods may overlook rare thalassemias or Hb variants. Long-read SMRT sequencing has the potential to identify breakpoints in fusion genes, demonstrating that it is a promising technique for detecting rare thalassemias.
Subject(s)
Hemoglobins, Abnormal , Thalassemia , Humans , Hemoglobins, Abnormal/genetics , Hemoglobins, Abnormal/analysis , Thalassemia/genetics , Multiplex Polymerase Chain Reaction , IndiaABSTRACT
In this report we decribed a new α-chain variant found during the measurement of hemoglobin A1c (Hb A1c) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an α-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A1c measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.
Subject(s)
Hemoglobins, Abnormal , Humans , Glycated Hemoglobin/genetics , Hemoglobins, Abnormal/genetics , Hemoglobins, Abnormal/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Chromatography, High Pressure Liquid , Electrophoresis, Capillary , Valine/geneticsABSTRACT
Autophagy is a well-conserved metabolic system that maintains homeostasis by relying on lysosomal breakdown. The endometrium of patients with intrauterine adhesion (IUA) and an animal model exhibits impaired autophagy. Autophagy is negatively correlated with inflammation. Activation of autophagy can inhibit the inflammatory response, while defects in autophagy will activate the inflammatory response. Here, we studied whether electroacupuncture (EA) inhibits inflammation and promotes endometrial injury repair by activating endometrial autophagy. The IUA animal model was established by mechanical injury plus lipopolysaccharide infection. EA stimulation was applied to the acupoints Guanyuan (CV4), bilateral Sanyinjiao (SP6), and Zusanli (ST36). The results indicated that EA could improve endometrial morphology, attenuate endometrial fibers, and enhance endometrial receptivity in the rat. EA could increase the autophagosomes of endometrial epithelial cells, increase the levels of LC3 and Beclin1, and decrease the level of p62. Additionally, EA may also suppress the nuclear factor kappa-B (NF-κB) signaling pathway and reduce the release of inflammatory factors. Additionally, the effect of EA was comparable to that of the autophagy agonist rapamycin, and the autophagy inhibitor 3-methyladenine reversed the therapeutic effect of EA. Therefore, we assume that EA may facilitate endometrial healing by activating autophagy and reducing NF-κB signal pathway-mediated inflammation.
Subject(s)
Electroacupuncture , Uterine Diseases , Humans , Female , Rats , Animals , NF-kappa B/metabolism , Signal Transduction/physiology , Uterine Diseases/therapy , Inflammation/therapy , AutophagyABSTRACT
Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Glucose Transporter Type 1 , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , MTOR Inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic useABSTRACT
Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act as constituents of metalloenzymes involved in cellular metabolism, function as signaling molecules to regulate the proliferation and metastasis of tumors, and are integral components of metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate the occurrence of programmed cell death (PCD), known as cuprotosis, in cancer cells. This modulation occurs through the disruption of tumor cell metabolism and the induction of proteotoxic stress. This discovery uncovers a mode of interaction between transition metals and proteins, emphasizing the intricate link between copper homeostasis and tumor metabolism. Moreover, they provide innovative therapeutic strategies for the precise diagnosis and treatment of malignant tumors. At the crossroads of chemistry and oncology, we undertake a comprehensive review of copper homeostasis in tumors, elucidating the molecular mechanisms underpinning cuproptosis. Additionally, we summarize current nanotherapeutic approaches that target cuproptosis and provide an overview of the available laboratory and clinical methods for monitoring this process. In the context of emerging concepts, challenges, and opportunities, we emphasize the significant potential of nanotechnology in the advancement of this field.
Subject(s)
Metalloproteins , Neoplasms , Transition Elements , Copper , Apoptosis , Nanotechnology , Neoplasms/drug therapyABSTRACT
OBJECT: Mycobacterium tuberculosis (MTB) is a bacterium that can cause zoonoses by aerosol transmission. Tuberculosis (TB) caused by MTB heavily burdens world public health security. Developing efficient, specific, convenient, and inexpensive MTB assays are essential for preventing and controlling TB. METHODS: In this study, we established a specific detection method for MTB using the Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) system, combined with recombinase mediated isothermal nucleic acid amplification (RAA) to improve the sensitivity of the detection system and achieve "two-level" amplification of the detection signal. The sensitivity and specificity of RAA combined with the CRISPR/Cas system were analyzed. Using BACTEC 960 culture as the gold standard for detecting MTB, we established the TB-CRISPR technique by testing 504 samples from patients with suspected TB. RESULTS: MTB H37Ra could be seen as low as 3.13 CFU/mL by the CRISPR-Cas12a system targeting IS6110. With BACTEC960 culture (120 positives and 384 negatives) as the gold standard, the sensitivity of the TB-CRISPR technique was 0.883 (0.809-0.932), and the specificity was 0.940 (0.910-0.961). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) reached 0.944 (0.914-0.975) within 95% CI. The positive likelihood ratio (PLR) was 14.747 (9.870-22.035), and the negative likelihood ratio (NLR) was 0.124 (0.076-0.203). The positive predictive value (PPV) was 0.822 (0.742-0.881), and the negative predictive value (NPV) was 0.963 (0.937-0.979). CONCLUSION: TB-CRISPR plays an essential role in the molecular diagnosis of TB. The whole detection time is less than 1.5 h. It is easy to operate and does not need complex instruments. It is of great significance for the rapid detection of MTB and the clinical diagnosis of TB.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Tuberculosis, Pulmonary/diagnosis , CRISPR-Cas Systems , Tuberculosis/diagnosis , Tuberculosis/microbiology , Sensitivity and SpecificityABSTRACT
Development of specific signal reporters with signal amplification effect are highly needed for sensitive and accurate detection of pathogen. Herein, we design a colorimetric immunosensing nanosystem based on liposome encapsulated quantum dots-sized MnO2 nanozyme (MnO2QDs@Lip) as a signal reporter for ultrasensitive and fast detection of SARS-CoV-2 antigen. The pathogenic antigens captured and separated by antibody-conjugated magnetic beads (MBs) are further connected with antibody-modified MnO2QDs@Lip to form a sandwich-like immunocomplex structure. After triggered release, MnO2 QDs efficiently catalyze colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB, which can be qualitatively observed by naked eyes and quantitatively analyzed by UV-Vis spectra or smartphone platforms. By taking advantages of immuno-magnetic separation, excellent peroxidase-like catalytic activity of MnO2 QDs, and high encapsulation efficiency of MnO2QDs@Lip, ultrasensitive detection of SARS-CoV-2 antigen ranging from 0.1 pg/mL to 100 ng/mL is achieved within 20 min. The limit of detection (LOD) is calculated to be 65 fg/mL in PBS buffer. Furthermore, real clinical samples of SARS-CoV-2 antigens can be effectively identified by this immunosensing nanosystem with excellent accuracy. This proposed detection nanosystem provides a strategy for simple, rapid and ultrasensitive detection of pathogens and may shed light on the development of new POCT detection platforms for early diagnosis of pathogens and surveillance in public health.
Subject(s)
Biosensing Techniques , Colorimetry , Immunoassay , SARS-CoV-2 , Colorimetry/methods , Biosensing Techniques/methods , Immunoassay/methods , Liposomes/chemistry , Antigens, Viral/analysis , Antigens, Viral/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/immunology , NanoparticlesABSTRACT
The demand for lactic acid and lactic acid-derived products in the food, pharmaceutical, and cosmetic industries is increasing year by year. In recent decades, the synthesis of lactic acid by microbials has gained much attention from scientists due to the superior optical purity of the product, its low production costs, and its higher production efficiency compared to chemical synthesis. Microbial fermentation involves the selection of feedstock, strains, and fermentation modes. Each step can potentially affect the yield and purity of the final product. Therefore, there are still many critical challenges in lactic acid production. The costs of feedstocks and energy; the inhibition of substrates and end-product; the sensitivity to the inhibitory compounds released during pretreatment; and the lower optical purity are the main obstacles hindering the fermentation of lactic acid. This review highlights the limitations and challenges of applying microbial fermentation in lactic acid production. In addition, corresponding solutions to these difficulties are summarized in order to provide some guidance for the industrial production of lactic acid.
ABSTRACT
Due to the unique and excellent biological, physical, and chemical properties of peptide hydrogels, their application in the biomedical field is extremely wide. The applications of peptide hydrogels are closely related to their unique responsiveness and excellent properties. However, its defects in mechanical properties, stability, and toxicity limit its application in the food field. In this review, we focus on the fabrication methods of peptide hydrogels through the physical, chemical, and biological stimulations. In addition, the functional design of peptide hydrogels by the incorporation with materials is discussed. Meanwhile, the excellent properties of peptide hydrogels such as the stimulus responsiveness, biocompatibility, antimicrobial properties, rheology, and stability are reviewed. Finally, the application of peptide hydrogel in the food field is summarized and prospected.
Subject(s)
Hydrogels , Peptides , Hydrogels/chemistry , Peptides/chemistry , Rheology , Food TechnologyABSTRACT
For the rational use of agricultural wastes, bagasse, orange peel and wheat bran were used to fabricate bio-based polymer materials. Cellulose was extracted from the three different agricultural wastes, and poly(ε-caprolactone) (PCL) was used as the matrix material. PCL was mixed with nanocrystalline cellulose (CNC), extracted bagasse cellulose (GC), orange peel cellulose (JC) and wheat bran cellulose (MC) by solution casting. Morphology and structure of the extracted cellulose were studied by Scanning Electron Microscope, Fourier Infrared spectrometer, thermogravimetry and X-ray diffractometer. The influence of GC, JC, MC on the crystallization process and mechanical properties of PCL was investigated by DSC and tensile test. Experimental results show that the addition of CNC, GC, JC, MC increases the crystallization temperature of PCL, accelerates the crystallization process of PCL, and improves the tensile property of PCL.
Subject(s)
Cellulose , Polyesters , Polyesters/chemistry , Cellulose/chemistry , Polymers/chemistry , Temperature , Dietary FiberABSTRACT
The microparticle-enhanced cultivation (MPEC) was used to enhance the production of Antrodin C by submerged fermentation of medicinal mushroom Antrodia cinnamomea. The crucial factors such as types, sizes, concentrations, and addition time of microparticles were optimized. The mechanism of MPEC on the membrane permeability and fluidity of A. cinnamomea and the expression of key genes in Antrodin C were investigated. When talc (18 µm, 2 g/L) was added into the fermentation liquid at 0 h, the promoting effect on Antrodin C was the best. The maximum yield of Antrodin C was 1615.7 mg/L, which was about 2.98 times of the control (541.7 mg/L). Talc slightly damaged the mycelia of A. cinnamomea, increased the release of intracellular constituents, and enhanced the index of unsaturated fatty acid. In addition, the key genes (IDI, E2.3.3.10, HMGCR, atoB) that might play an important role in the synthesis of the triquine-type sesquiterpene Antrodin C, were upregulated. In conclusion, talc increased the permeability and fluidity of cell membrane, upregulated the key genes and improved the biosynthesis process to enhance the yield of Antrodin C in the submerged fermentation of A. cinnamomea.
Subject(s)
Agaricales , Antrodia , Talc/metabolism , Antrodia/genetics , Antrodia/metabolismABSTRACT
The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) proteins constitute the innate adaptive immune system in several bacteria and archaea. This immune system helps them in resisting the invasion of phages and foreign DNA by providing sequence-specific acquired immunity. Owing to the numerous advantages such as ease of use, low cost, high efficiency, good accuracy, and a diverse range of applications, the CRISPR-Cas system has become the most widely used genome editing technology. Hence, the advent of the CRISPR/Cas technology highlights a tremendous potential in clinical diagnosis and could become a powerful asset for modern medicine. This study reviews the recently reported application platforms for screening, diagnosis, and treatment of different diseases based on CRISPR/Cas systems. The limitations, current challenges, and future prospectus are summarized; this article would be a valuable reference for future genome-editing practices.
ABSTRACT
Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis and high mortality rate worldwide. Glucose metabolism disorder is one of the most important characteristics of HCC. However, as the primary risk factors for the prognosis of HCC patients are unclear, the survival prognosis and therapy response of patients cannot be accurately predicted. Methods: First, gene sets of 29 cancer hallmarks were collected from public databases. The z-score of various cancer hallmarks were quantitively analyzed by a single-sample gene set enrichment analysis (ssGSEA) of HCC patients. Next, a glycolysis-related gene signature (GRS) was constructed using a series of bioinformatics methods, which were used to predict the survival prognosis of HCC patients and the immunotherapy benefits. The prediction accuracy of the GRS was validated in different HCC cohorts and clinical subgroups. Additionally, a decision tree and nomogram were also established based on the GRS and other clinical variables. Finally, the genomic alterations and tumor immune microenvironment of the HCC patients were examined. Results: Among the 29 cancer hallmarks, glycolysis was the most predominant risk factor for a poor prognosis in HCC. We subsequently constructed a novel GRS comprising 12 glycolysis-related genes. The high-GRS patients had a poorer survival prognosis than the low-GRS patients. The GRS exhibited a powerful ability to predict survival prognosis in different HCC cohorts and clinical feature subgroups. Additionally, the decision tree and nomogram aided in the risk stratification and prognosis evaluations of HCC patients. Further, we found that a high GRS was characterized by a severe tumor stage, pathological grade, and other clinical features. There were significant differences in the genomic alterations, immune cells, and immune checkpoints between the low- and high-GRS patients, especially in relation to the tumor protein p53 mutation and immunosuppressive cells. Notably, we also found that the GRS could be used to identify HCC patients who are more sensitive to chemotherapy and immunotherapy. Conclusions: In summary, the GRS may be a useful tool for predicting the prognosis and guiding the clinical therapy of HCC patients.
ABSTRACT
Gastrointestinal cancer is one of the most common malignancies with relatively high morbidity and mortality. Exosomes are nanosized extracellular vesicles derived from most cells and widely distributed in body fluids. They are natural endogenous nanocarriers with low immunogenicity, high biocompatibility, and natural targeting, and can transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA, proteins, lipids, and other bioactive components, which can play a role in information transmission and regulation of cellular physiological and pathological processes during the progression of gastrointestinal cancer. In this paper, the role of exosomes in gastrointestinal cancers is briefly reviewed, with emphasis on the application of exosomes as drug delivery systems for gastrointestinal cancers. Finally, the challenges faced by exosome-based drug delivery systems are discussed.
ABSTRACT
BACKGROUND: Cases of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection have been increasing. Patients with MRSA bloodstream infection have a poor prognosis and high mortality rate. Identification of potential risk factors associated with MRSA bloodstream infection-related mortality may help improve patient outcomes. METHODS: Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with MRSA bloodstream infections. Two investigators independently assessed articles for inclusion and data extraction. RESULTS: Twenty observational studies were included in the analysis. Factors associated with higher mortality were development of severe sepsis or septic shock [odds ratio (OR): 4.56, 95% CI: 3.37-6.18], congestive heart failure (OR: 1.78, 95% CI: 1.27-2.50), liver cirrhosis (OR: 1.90, 95% CI: 1.27-2.65), malignancy (OR: 1.62, 95% CI: 1.33-1.98), infective endocarditis (OR: 2.05, 95% CI: 1.35-3.11), nosocomial infection (OR: 2.80, 95% CI: 1.41-5.55), intensive care unit admission (OR: 3.08, 95% CI: 1.49-6.36) and inappropriate empirical antimicrobial treatment (OR: 2.25, 95% CI: 1.16-4.36); removal of the eradicable foci was a protective factor (OR: 0.51, 95% CI: 0.40-0.63) The average APACHE II score at the time of diagnosis of MRSA bloodstream infection was considerably higher in patients who did not survive than in those who survived [weighted mean difference (WMD): 5.81, 95% CI: 3.03-8.59]. DISCUSSION: Patient condition, appropriate timing of antimicrobial treatment, surgical intervention and disease severity according to the APACHE II score are the most important risk factors for death in patients with MRSA bloodstream infections.
Subject(s)
Cross Infection , Methicillin-Resistant Staphylococcus aureus , Sepsis , Staphylococcal Infections , Adult , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Humans , Risk Factors , Staphylococcal Infections/drug therapyABSTRACT
Morphology plays an important role in fungal fermentation and secondary metabolites biosynthesis. One novel technique, microparticle-enhanced cultivation was successfully utilized to control the morphology of Monascus purpureus precisely and enhance the yield of yellow pigments. The production of yellow pigments increased to 554.2 U/ml when 4 g/L 5000 mesh talc added at 24 h. Field emission scanning electron microscope observation indicated that the actual effect depends on the properties of microparticle. Sharp-edged microparticles showed better stimulatory effects than smooth, round-shaped ones. Particle size analysis, scanning electron microscope, and cell integrity evaluation proved obvious morphological changes were induced by talc addition, including smaller mycelial size, rougher hyphae, and decreased cell integrity. Furthermore, the expression levels of MrpigG, MrpigD, MrpigE, and MrpigH were significantly upregulated by the addition of talc. It indicated that the microparticle could not only affect the mycelial morphology, but also influence the expression levels of key genes in biosynthetic pathway of Monascus yellow pigments.