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Biomedical subjects

Min Cao

Publications and source records attributed to Min Cao.

At least 19 recordsLinked to original sources
PubMed2026

Cross-target and cell-preferential CRISPR-Cas9 inhibition with carbohydrate-tagged oligonucleotides.

Precise control of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) activity is important for limiting off-target effects and chromosomal rearrangements. Existing inhibitors, including anti-CRISPR proteins and spacer-targeting oligonucleotides, can be constrained by immunogenicity, target-sequence dependence, or delivery challenges. Here, we developed single-stranded DNA oligonucleotides that target conserved regions of the Streptococcus pyogenes Cas9 single-guide RNA (sgRNA) scaffold rather than the variable spacer. Screening identified single-stranded DNA 7 (ssDNA7), which targets stem-loop-1 and the adjacent linker and inhibits Cas9 activity across multiple tested spacer sequences and genomic loci without redesigning the inhibitor. Carbohydrate conjugation improved oligonucleotide stability and preferentially enhanced inhibitory activity in selected liver-derived or cancer cell models. Amplicon sequencing confirmed inhibition of endogenous editing in multiple cell models and normal liver-derived organoids, and supported cell-preferential inhibition in matched cell comparisons. These findings establish sgRNA-scaffold targeting as a strategy for cross-target inhibition of Cas9 and show that carbohydrate conjugation can tune its cellular activity.

CRISPR-Cas9↗
PubMed2026

Construction of circRNA-miRNA-mRNA regulatory networks in the intestine of turbot (Scophthalmus maximus) following Vibrio anguillarum infection.

Circular RNAs (circRNAs) play pivotal roles in post-transcriptional regulation by acting as molecular sponges for microRNAs (miRNAs) within the competitive endogenous RNA (ceRNA) network. However, the regulatory mechanisms in teleost immune responses remain poorly understood. In this study, circRNA-miRNA-mRNA networks were investigated in turbot (Scophthalmus maximus) following Vibrio anguillarum infection to elucidate host-pathogen interactions. Through high-throughput sequencing of intestinal tissues, a total of 50 differentially expressed circRNAs (DE-circRNAs) (18 at 2 hpi, 16 at 12 hpi, 16 at 48 hpi), 212 DE-miRNAs (11 at 2 hpi, 70 at 12 hpi, 15 at 48 hpi), and 1774 DE-mRNAs were identified. Functional enrichment analyses (GO/KEGG) revealed significant associations with immune pathways, including the MAPK signaling pathway and gap junction. An integrated circRNA-miRNA-mRNA regulatory network was constructed, highlighting key interactions including novel_circ_0002573/DE-miR-27a-3p/FGB and novel_circ_0002423/novel_347/GNE, which may regulate inflammatory and antibacterial responses. The expression patterns of selected circRNAs, miRNAs and mRNAs were validated using qRT-PCR, confirming the reliability of the sequencing results. Importantly, fibrinogen beta chain (FGB) and CXCR4/CXCL12 signaling were identified as critical immune modulators. These findings provide insights of the ceRNA regulatory networks involved in teleost intestinal immunity and provide potential molecular targets for selective breeding of disease resistance in this species.

Animals↗
PubMed2025

Structure-activity relationships study on inhibition of CRISPR-Cas9 by glycosaminoglycans.

The CRISPR-Cas9 system is a revolutionary genome editing system known for its precision, simplicity and efficiency, playing a crucial role in gene-editing. It has enabled applications ranging from biomedicine to agriculture. However, the uncontrollable activity of Cas9 has raised significant safety concerns in clinical settings, limiting its broader application. Consequently, regulating CRISPR-Cas9 activity holds substantial promise for enhancing the safety and efficacy of gene-editing technologies. In this study, we demonstrated that sulfated glycosaminoglycans (GAGs) exhibit inhibitory effects of Cas9. Specifically, both chondroitin sulfate (CS) and heparin (HP) can inhibit CRISPR/Cas9 activity, with heparin showing a stronger inhibitory effect that correlates positively with its concentration. Molecular dynamics simulations indicate that sulfated heparin residues might inhibit Cas9 function by binding to essential DNA-binding sites, which are crucial for functional interactions, potentially impairing activity. Additionally, higher molecular weight GAGs exhibit enhanced inhibitory effects under the same sulphation. Notably, the sulfation site also influenced activity. C6-sulfation of chondroitin sulfate is more favorable for Cas9 inhibition, and N-sulfation of heparin enhances its inhibitory effect on Cas9 activity. These findings provide valuable insights into the development of carbohydrate-based inhibitors for CRISPR-Cas9, offering a foundation for further exploration in this field.

CRISPR-Cas Systems↗
PubMed2006

Optimization of atrioventricular delay by surface electrocardiography during dual chamber pacing.

BACKGROUND: Nominal atrioventricular (AV) interval in dual chamber pacemaker (DDD) is not the best AV delay in the majority of patients with atrioventricular block. To find a simple method for optimizing AV delay adjustment, we assessed surface electrocardiography (ECG) for optimizing AV delay during dual chamber pacing. METHODS: DDD pacemakers were implanted in 46 patients with complete, or almost complete, AV block. Optimal AV delay was achieved by programming an additional delay of 100 ms, to the width of intrinsic P wave or to the interval between pacing spike to the end of P wave on surface ECG. Left ventricular (LV) end diastolic and end systolic volumes, ejection fraction and diastolic parameters were measured by Doppler echocardiography during both nominal and optimal AV delay pacing. RESULTS: Compared to nominal AV delay setting, LV end diastolic volume increased [to (53.2 +/- 11.3) ml from (50.2 +/- 10.2) ml, P < 0.05], end systolic volume decreased [to (26.1 +/- 9.0) ml from (27.9 +/- 8.2) ml, P < 0.05] during adjusted AV delay pacing, resulting in an increase in LV ejection fraction [to (68.2 +/- 5.3)% from (64.5 +/- 4.3)%, P < 0.05]. LV diastolic filling and isovolumic relaxation time were not significantly changed. CONCLUSION: Optimization of AV delay by surface ECG is a simple method to improve LV systolic function during dual chamber pacing.

Adult↗
PubMed2006

[Determination of cotinine in human urine with gas chromatograph-mass spectrometry].

OBJECTIVE: To establish the method of gas chromatograph-mass spectrometry (GC-MS) for the determination of the cotinine (COT) in human urine. METHODS: The conjugated trans-3'-hydroxycotinine (THOC) and COT were hydrolyzed in human urine with beta-glucuronidase. The composition of COT was extracted with the mixture of dichloromethane and n-butyl acetate (2:1) and was separated with HP-5MS fused-silica capillary column. The GC-MS was used for determining its content. RESULTS: The monitoring limit of this method was 0.02 microg/L. Its recovery rate was higher than 90%, Its accuracy rate was 4.30%. It was used for the determination of the cotinine in human urine in Guangzhou Biological Bank the Elderly Cohort. CONCLUSION: The GC-MS method is a good microanalysis for monitoring the cotinine in human urine rapidly and accurately with little background disturbance. It has been applied in our Guangzhou Cohort Study for determining cotinine in human urine.

Cotinine↗
PubMed2006

[Giant cell interstitial pneumonia: a case report and literature review].

OBJECTIVE: To highlight the characteristics of giant cell interstitial pneumonia (GIP). METHODS: The clinical, radiological and pathological data of a patient with GIP confirmed by open lung biopsy were presented, and relevant literatures were reviewed. RESULTS: Patients with GIP usually had a history of exposure to metal dust. Clinical presentations include cough and dyspnea on exertion, and pulmonary function testing showed a restrictive abnormality. On chest radiography and high-resolution CT scans, it presents as bilateral areas of ground-glass attenuation, areas of consolidation, diffuse small nodules, extensive reticular opacities and traction bronchiectasis. The main pathological findings include a desquamative interstitial pneumonia (DIP)-like reaction with intra-alveolar macrophages and numerous large multinucleated histiocytes that ingested inflammatory cells were admixed with macrophages. The finding of GIP is almost pathognomonic for hard metal pneumoconiosis. CONCLUSIONS: GIP is a very rare chronic interstitial pneumonia, and has no characteristic clinical manifestations. Radiographic findings are similar to other idiopathic interstitial pneumonias. Meticulous history taking on occupational exposure is important for the diagnosis of GIP.

Biopsy↗
PubMed2006

[A prospective cohort study on comparison of risk of death of respiratory system diseases between occupational dust exposure and smoking].

OBJECTIVE: To compare the effects of dust exposure and smoking on mortality of respiratory system diseases (RSD). METHODS: Based on the Guangzhou Occupational Health Surveillance Record System established between 1989 and 1992, 80,987 factory workers, aged 30 years old or older, occupationally exposed or not exposed to dusts, were included in a prospective cohort study. RESULTS: (1) The mean age of the cohort was 43.5. Most subjects were workers, had secondary education, and almost all were married. The dust exposure rate was 16.3%, the smoking rate 43.7% and the alcohol-drinking rate 33.5%. (2) The cohort was followed up for 8 years on average, but 35 people (0.04%) were lost for follow up. Among the 1593 deaths, 219 and 90 people died of lung cancer and non-cancer respiratory system diseases (NCRSD) respectively. (3) The adjusted relative risk (RR) of death of lung cancer for smokers, 3.32, was 2.2 times of that for dust exposed workers, 1.53, and the RR of death of NCRSD for dust exposed workers, 2.41, 1.28 times of that for smokers, 1.89, especially for silica dust-exposed workers, 5.72, 3.03 times of that for smokers. Dust exposure combined with smoking caused significantly higher RR of death of RSD. (4) In male, the death risks of RSD were increased with the amount of smoking per day and years of smoking. CONCLUSION: Occupational dust exposure and smoking may cause excessive lung cancer and NCRSD death with synergistic effects. Smoking has higher RR of Lung cancer death than dust exposure. However, the dust exposure contributes to higher RR of NCRSD death. There is a significant dose-effect relationship between smoking and the death risk of RSD.

Adult↗
PubMed2006

[Study of blending method for the extracts of herbal plants].

The irregularity in herbal plant composition is influenced by multiple factors. As for quality control of traditional Chinese medicine, the most critical challenge is to ensure the dosage content uniformity. This content uniformity can be improved by blending different batches of the extracts of herbal plants. Nonlinear least-squares regression was used to calculate the blending coefficient, which means no great absolute differences allowed for all ingredients. For traditional Chinese medicines, even relatively smaller differences could present to be very important for all the ingredients. The auto-scaling pretreatment was used prior to the calculation of the blending coefficients. The pretreatment buffered the characteristics of individual data for the ingredients in different batches, so an improved auto-scaling pretreatment method was proposed. With the improved auto-scaling pretreatment, the relative. differences decreased after blending different batches of extracts of herbal plants according to the reference samples. And the content uniformity control of the specific ingredients could be achieved by the error control coefficient. In the studies for the extracts of fructus gardeniae, the relative differences of all the ingredients is less than 3% after blending different batches of the extracts. The results showed that nonlinear least-squares regression can be used to calculate the blending coefficient of the herbal plant extracts.

Drugs, Chinese Herbal↗
PubMed2006

[An integrated method works well on varicocele].

OBJECTIVE: To assess an integrated method of operation + Chinese medicine + dexamethasone + vitamin E in treating varicocele. METHODS: Ninety-six patients with varicocele were randomly divided into two groups, the experimental group (Group A, n=47) treated with the integrated method, the control group (Group B, n=49) treated with Chinese medicine, dexamethasone and vitamin E. RESULTS: After the treatment, the sperm density and motility and pregnancy rate were higher (P < 0.01 or P < 0.05) and the sperm deformity rate was lower in the experiment group than in the control (P < 0.05). CONCLUSION: The integrated method works better than either operation or Chinese medicine applied alone in the treatment of varicocele.

Adult↗
PubMed2005

Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery.

Currently, there is a need for therapeutic vaccines that are effective in inducing robust T helper type 1 (Th1) immune responses capable of mediating viral clearance in chronic hepatitis B infection. Hepatitis B therapeutic vaccines were designed and formulated by loading the hepatitis B core antigen (HBcAg) into poly(D,L-lactic-acid-co-glycolic acid) (PLGA) nanoparticles with or without monophospholipid A (MPLA), a Th1-favoring immunomodulator. These particles were around 300 nm in diameter, spherical in shape and had approximately 50% HBcAg encapsulation efficiency. A single immunization with a vaccine formulation containing (MPLA+HBcAg) coformulated in PLGA nanoparticles induced a stronger Th1 cellular immune response with a predominant interferon-gamma (IFN-gamma) profile than those induced by HBcAg alone, free (HBcAg+MPLA) simple mixture or HBcAg-loaded nanoparticles in a murine model. More importantly, the level of HBcAg-specific IFN-gamma production could be increased further significantly by a booster immunization with the (HBcAg+MPLA)-loaded nanoparticles. In summary, these results demonstrated that codelivery of HBcAg and MPLA in PLGA nanoparticles promoted HBcAg-specific Th1 immune responses with IFN-gamma production. These findings suggest that appropriate design of the vaccine formulation and careful planning of the immunization schedule are important in the successful development of effective HBV therapeutic vaccines.

Adjuvants, Immunologic↗
PubMed2005

Bacillus subtilis paraquat resistance is directed by sigmaM, an extracytoplasmic function sigma factor, and is conferred by YqjL and BcrC.

A Bacillus subtilis sigM null mutant, lacking the extracytoplasmic function sigma(M) protein, was sensitive to paraquat (PQ), a superoxide-generating reagent, but not to the redox stress-inducing compounds hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide, or diamide. Surprisingly, a sigM mutant was only sensitive to superoxide-generating compounds with a dipyridyl ring such as PQ, ethyl viologen, benzyl viologen, and diquat but not to menadione, plumbagin, pyrogallol, or nitrofurantoin. Mutational analysis of candidate sigma(M)-regulated genes revealed that both YqjL, a putative hydrolase, and BcrC, a bacitracin resistance protein, were involved in PQ resistance. Expression of yqjL, but not bcrC, from a xylose-inducible promoter restored PQ resistance to the sigM mutant.

ATP-Binding Cassette Transporters↗
PubMed2005

Design and development of a DNA array for rapid detection and genotyping of seven kinds of pathogenic microbes.

A DNA array for rapid detection and genotyping of the pathogenic microbes of epidemic hemorrhagic fever, tsutsugamushi disease, leptospirosis, malaria, schistosomiasis, cholera, and hemorrhagic colitis was developed. The specific and relatively conserved PCR primers and DNA probes were screened from the characteristic genes of the pathogenic microbes. The PCR or RT-PCR methods were established for amplifying and labeling the DNA fragments of the pathogenic microbes. All the probes with the same Tm value were synthesized chemically and modified with an NH2 at their 5' terminus, they were printed on glass slides for fabrication of a oligonucleotide DNA array. The developed DNA array could be used for detecting and genotyping the pathogenic microbes simultaneously, and they had a high sensitivity and specificity.

Animals↗
PubMed2004

Characterization of poly(D,L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells.

Biodegradable nanoparticles made of poly(D,L-lactic acid-co-glycolic acid) (PLGA) copolymer were characterized for enhanced delivery of antigens to murine bone marrow derived dendritic cells (DCs) in vitro. PLGA nanoparticles were efficiently phagocytosed by the DCs (CD11c+, MHC class II+, CD86+) in culture, resulting in their intracellular localization. The efficiency of the uptake was influenced by the incubation time and nanoparticle concentration. DCs pulsed with PLGA nanoparticles containing an immunomodulator, monophosphoryl lipid A (MPLA), showed upregulation of surface expression of MHC class II and CD86 molecules. Delivery of a cancer-associated antigen (MUC1 mucin peptide: BLP25) and MPLA in PLGA nanoparticles was shown to be superior to their delivery in the soluble form for activation of naïve T cells of normal and MUC1-transgenic mice. These results strongly suggest that PLGA nanoparticles provide an efficient vaccine delivery system for targeting DCs and the development of DC based cellular vaccines.

Animals↗
PubMed2004

The Bacillus subtilis extracytoplasmic-function sigmaX factor regulates modification of the cell envelope and resistance to cationic antimicrobial peptides.

Bacillus subtilis contains seven extracytoplasmic-function sigma factors that activate partially overlapping regulons. We here identify four additional members of the sigma(X) regulon, pbpX (penicillin-binding protein), ywnJ, the dlt operon (D-alanylation of teichoic acids), and the pss ybfM psd operon (phosphatidylethanolamine biosynthesis). Modification of teichoic acids by esterification with D-alanine and incorporation of phosphatidylethanolamine into the cell membrane have a common consequence: in both cases positively charged amino groups are introduced into the cell envelope. The resulting reduction in the net negative charge of the cell envelope has been previously implicated as a resistance mechanism specific for cationic antimicrobial peptides. Consistent with this notion, we find that both sigX and dltA mutants are more sensitive to nisin than wild-type cells. We conclude that activation of the sigma(X) regulon serves to alter cell surface properties to provide protection against antimicrobial peptides.

Antimicrobial Cationic Peptides↗
PubMed2004

Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery.

The main objective of these studies was to investigate whether the nanoparticle delivery has any immunopotentiation effect at modest doses of a few micro- or nanograms of CpG oligodeoxynucleotide (CpG ODN) and what would be the influence on T cell responses at such low doses. Various doses (5 to 0.05 microg) of a model CpG ODN adjuvant (#1826) along with 2 Lf tetanus toxoid (TT) were formulated in either nanoparticles using poly(D,L-lactic-co-glycolic acid) (PLGA) 50:50 co-polymer, or saline. Strong antigen specific ex vivo T cell proliferation was observed for the Balb/c mice receiving immunogens in nanoparticles. At 5 microg dose of CpG ODN, the T cell stimulation index (SI) was 241 as compared with 74 for the same dose when given in saline. Comparable SI value of 78 was observed at 100-fold lower dose (0.05 microg) using nanoparticles. Similarly, significantly higher (P<0.01) cytokine secretion was observed for nanoparticles groups. A ten-fold lower dose (0.5 microg instead of 5 microg) of CpG ODN in nanoparticles was adequate to obtain levels of IFN-gamma, TNF-alpha, and IL-2 comparable to those observed following immunisations in saline. The immunopotentiation effect of the particulate delivery on antibody response (total IgG and subtypes) was not so marked. These studies emphasise that antigen delivery in biodegradable nanoparticles can facilitate induction of strong T cell responses, particularly of the Th1 type, at extremely lower doses of CpG ODN. Such reduction in the effective dose would be advantageous for minimising the potential side effects of these novel adjuvants.

Adjuvants, Immunologic↗