Diagnostic accuracy of tumor necrosis factor-alpha, interferon-gamma, interlukine-10 and adenosine deaminase 2 in differential diagnosis between tuberculous pleural effusion and malignant pleural effusion

BACKGROUND: The current study was performed to investigate the potential biomarkers for the differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusions (MPE). METHODS: Among ninety patients (n = 90) involved in the study, 47 with tuberculous pleural effusion aged from 18 to 70 and 43 with secondary malignant pleural effusion aged from 34 to 78. We tested the pleural levels of TNF-α, IFN-γ and IL-10 as well as the enzyme activity of ADA(2), and then we compared the differential diagnostic efficiencies of those biochemical parameters with ADA between the two groups. RESULTS: Our results show that, the concentrations of pleural TNF-α (45.55 ± 15.85 ng/L), IFN-γ (114.97 ± 27.85 ng/L) as well as activities of ADA(2) (35.71 ± 10.00 U/L) and ADA (39.39 ± 10.60 U/L) in tuberculous group were significantly higher compared to malignant group. Furthermore, according to the ROC curve analysis the thresholds of TNF-α, IFN-γ, ADA(2) and ADA were found to be 30.3 ng/L, 103.65 ng/L, 29.45 U/L, and 39.00 U/L, respectively. TNF-α, IFN-γ and ADA(2) yielded better sensitivity, specificity, and accuracy of the diagnosis than ADA. Our investigation further revealed that the combinations of TNF-α and ADA(2) further increased the specificity and accuracy for the differential diagnosis. CONCLUSION: In conclusion, we found that TNF-α, IFN-γ, ADA and ADA(2) all increased in TPE. Combinations of the TNF-α and ADA(2) yielded the best specificity and accuracy for the differential diagnosis of TPE from MPE. Our investigation suggests that the applications of TNF-α together with ADA(2) may contribute to more efficient diagnosis strategies in the management of discrimination between tuberculous and malignant pleural effusions

Screening of the LTBP2 gene in 214 Chinese sporadic CYP1B1-negative patients with primary congenital glaucoma

Purpose To identify deleterious mutations in the latent transforming growth factor-β–binding protein 2 (LTBP2) gene in sporadic patients with primary congenital glaucoma (PCG) from a Han Chinese population, which had been excluded for mutations in the CYP1B1 gene. Methods: In this retrospective case–control study, 36 coding exons and adjacent exon–intron boundaries of LTBP2 were amplified with PCR and screened for mutations with Sanger sequencing in DNA samples of 214 sporadic patients with PCG. Sequence variants identified in the patients with PCG were subsequently screened in 100 unaffected control subjects and the unaffected parents of the patients with PCG who had sequence changes in LTBP2. Results: Eight heterozygous single nucleotide polymorphisms (SNPs) in coding regions of LTBP2 were identified in the patients with PCG. Four of these SNPs were missense changes that resulted in the replacement of amino acids (rs2304707, rs116914994, rs45468895, and rs763035721), two of which (rs2304707 and rs116914994) were also present in the control subjects. No significant differences in the frequencies of the missense SNPs were found between the patients with PCG and the controls. The two missense SNPs, rs45468895 and rs763035721, which were each found in one patient also existed in their unaffected parents, suggesting that these two SNPs were not segregated in these families and are unlikely to be a disease-causative variant. In addition, four synonymous SNPs were detected in the patients with PCG (rs61738025, rs862031, rs199805158, and rs12586758). Conclusions: The results showed that no deleterious mutations were found in coding regions of LTBP2 in patients with PCG, suggesting that it is not a causal gene for PCG in the Han Chinese population

M6A methylation of DEGS2, a key ceramide-synthesizing enzyme, is involved in colorectal cancer progression through ceramide synthesis.

N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulator in cancer. However, the understanding of m6A modification on lipid metabolism regulation in colorectal cancer (CRC) is very limited. Here, we observed that human CRCs exhibited increased m6A mRNA methylation mediated by dysregulation of m6A erasers and readers. By performing methylated RNA-immunoprecipitation sequencing (MeRIP-seq) and transcriptomic sequencing (RNA-seq), we identified DEGS2 as a downstream target of m6A dysregulation. Overexpression or knockdown of DEGS2 confirmed the role of DEGS2 in proliferation, invasion and metastasis of CRC both in vitro and in vivo. Mechanistic studies identified the specific m6A modification site within DEGS2 mRNA, and mutation of this target site was found to drastically enhance the proliferative and invasive ability of CRC cells in vitro and promote tumorigenicity in vivo. Lipidome analysis showed that lipid metabolism was dysregulated in CRC. Moreover, ceramide synthesis was suppressed due to DEGS2 upregulation mediated by m6A modification in CRC tissues. Our findings highlight that the function of DEGS2 m6A methylation in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology

In Vitro Effects of Spectinomycin and Ceftriaxone Alone or in Combination with Other Antibiotics against Chlamydia trachomatis

The in vitro effects of spectinomycin and ceftriaxone, alone or in combination with erythromycin, ofloxacin, and doxycycline, against Chlamydia trachomatis were investigated by the checkerboard method and compared by Ridit (reference identical unit) analysis. A combination of spectinomycin with erythromycin or doxycycline was found to be more effective than that of ceftriaxone

Speciation, Fate and Transport, and Ecological Risks of Cu, Pb, and Zn in Tailings from Huogeqi Copper Mine, Inner Mongolia, China

Tailings collected from the tailing reservoir at Huogeqi Copper Mine, located in Inner Mongolia, China, were used in a leachate study to evaluate the acid potential, neutralization potential, and possibility for producing acid mine drainage (AMD) from the site. The speciation of Cu, Pb, and Zn contained in the tailings was also determined during the leachate study to further access the potential migration abilities of these metals. The results showed that the tailings did not produce significant AMD as the pH of the leachate ranged from 7 to 9 and decreased with time. The Cu, Pb, and Zn concentrations were high, ranging from 439.1 to 4527 mg/kg in the tailings and from 0.162 to 7.964 mg/L in the leachate, respectively. Concentrations of metals in the leachate and tailings were positively correlated. Over 60% of the Cu in the tailing samples existed in an oxidizable form. Most of the Pb also existed in its oxidized form, as did the silicate and Zn. Metals usually have higher mobility in their exchangeable and oxidizable forms and as such represent a higher potential risk to the environment. Results of risk assessment code also revealed that metals in tailings exerted medium to high risks to the environment

NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc

Abstract Diffuse large B-cell lymphoma (DLBCL) is malignant hyperplasia of B lymphocytes and standard care cannot satisfactorily meet clinical needs. Potential diagnostic and prognostic DLBCL biomarkers are needed. NCBP1 could bind to the 5ʹ-end cap of pre-mRNAs to participate in RNA processing, transcript nuclear export and translation. Aberrant NCBP1 expression is involved in the pathogenesis of cancers, but little is known about NCBP1 in DLBCL. We proved that NCBP1 is significantly elevated in DLBCL patients and is associated with their poor prognosis. Then, we found that NCBP1 is important for the proliferation of DLBCL cells. Moreover, we verified that NCBP1 enhances the proliferation of DLBCL cells in a METTL3-dependent manner and found that NCBP1 enhances the m6A catalytic function of METTL3 by maintaining METTL3 mRNA stabilization. Mechanistically, the expression of c-MYC is regulated by NCBP1-enhanced METTL3, and the NCBP1/METTL3/m6A/c-MYC axis is important for DLBCL progression. We identified a new pathway for DLBCL progression and suggest innovative ideas for molecular targeted therapy of DLBCL

Actional Mechanisms of Active Ingredients in Functional Food Adlay for Human Health

Medicinal and food homologous adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases

Homodimer-mediated phosphorylation of C/EBPα-p42 S16 modulates acute myeloid leukaemia differentiation through liquid-liquid phase separation

Abstract CCAAT/enhancer binding protein α (C/EBPα) regulates myeloid differentiation, and its dysregulation contributes to acute myeloid leukaemia (AML) progress. Clarifying its functional implementation mechanism is of great significance for its further clinical application. Here, we show that C/EBPα regulates AML cell differentiation through liquid-liquid phase separation (LLPS), which can be disrupted by C/EBPα-p30. Considering that C/EBPα-p30 inhibits the functions of C/EBPα through the LZ region, a small peptide TAT-LZ that could instantaneously interfere with the homodimerization of C/EBPα-p42 was constructed, and dynamic inhibition of C/EBPα phase separation was observed, demonstrating the importance of C/EBPα-p42 homodimers for its LLPS. Mechanistically, homodimerization of C/EBPα-p42 mediated its phosphorylation at the novel phosphorylation site S16, which promoted LLPS and subsequent AML cell differentiation. Finally, decreasing the endogenous C/EBPα-p30/C/EBPα-p42 ratio rescued the phase separation of C/EBPα in AML cells, which provided a new insight for the treatment of the AML