Role of non-coding RNAs mediated pyroptosis on cancer therapy: a review.

INTRODUCTION: Non-coding RNAs (ncRNAs), which are incapable of encoding proteins, are involved in the progression of numerous tumors by altering transcriptional and post-transcriptional processing. Recent studies have revealed prominent features of ncRNAs in pyroptosis, a type of non-apoptotic programmed cellular destruction linked to an inflammatory reaction. Drug resistance has arisen gradually as a result of anti-apoptotic proteins, therefore strategies based on pyroptotic cell death have attracted increasing attention. We have observed that ncRNAs may exert significant influence on cancer therapy, chemotherapy, radio- therapy, targeted therapy and immunotherapy, by regulating pyroptosis. AREAS COVERED: Literatures were searched (December 2023) for studies on cancer therapy for ncRNAs-mediated pyroptotic cell death. EXPERT OPINION: The most universal mechanical strategy for ncRNAs to regulate target genes is competitive endogenous RNAs (ceRNA). Besides, certain ncRNAs could directly interact with proteins and modulate downstream genes to induce pyroptosis, resulting in tumor growth or inhibition. In this review, we aim to display that ncRNAs, predominantly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), could function as potential biomarkers for diagnosis and prognosis and produce new insights into anti-cancer strategies modulated by pyroptosis for clinical applications.

Huaier suppresses cell viability, migration and invasion in human non-small cell lung cancer via lncRNA DLEU2/miR-212-5p/ELF3 axis.

Accumulating studies suggest that Huaier exerts anti-tumor effects through intricate mechanisms. Despite extensive research on its efficacy in lung cancer, further investigation is required to elucidate the molecular mechanism of Huaier. The involvement of long noncoding RNAs (lncRNAs) in the anti-lung cancer effects of Huaier remains unknown. In this study, we found Huaier suppressed cell viability, migration and invasion in non-small cell lung cancer (NSCLC) cells. LncRNA sequencing analysis revealed Deleted in lymphocytic leukemia 2 (DLEU2) to be significantly downregulated in Huaier-treated NSCLC cells. Furthermore, DLEU2 silencing was observed to suppress NSCLC progression, while DLEU2 overexpression attenuated the anti-tumor effects of Huaier in NSCLC, thereby promoting cell viability, migration and invasion of NSCLC. The ceRNA role of DLEU2 had been demonstrated in NSCLC, which directly interacted with miR-212-5p to rescue the repression of E74 Like ETS Transcription Factor 3 (ELF3) by this microRNA. Additionally, Huaier was found to regulate the expression of miR-212-5p and ELF3. Functionally, miR-212-5p inhibitor or ELF3 overexpression reversed the effects of DLEU2 silencing or Huaier treatment, resulting in increased colony formation, migration and invasion in NSCLC. Taken together, these results illuminate the mechanism underlying Huaier's anti-tumor effects via the DLEU2/miR-212-5p/ELF3 signaling pathway, which offers novel insights into the anti-tumor effects of Huaier and constitutes a promising therapeutic target for the treatment in NSCLC.

Bacteremia caused by Comamonas kerstersii in a patient with acute perforated appendicitis and localized peritonitis: case report and literature review.

Comamonas kerstersii (C. kerstersii) is a Gram-negative bacterium that was initially thought to be non-pathogenic to humans and is abundant in the environment. In recent years, with the availability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) that enable fast and accurate bacterial identification, there have been increasing number of reports of human infections caused by C. kerstersii, indicating that this organism has emerged as human pathogen. In fact, most clinical isolates of C. kerstersii are recovered from peritoneal liquid, and bacteremia has been infrequently reported. Here, we report a case of bacteremia caused by C. kerstersii in a 28-year-old male patient with acute perforated appendicitis and localized peritonitis and present a comprehensive review of C. kerstersii infections in pathogenic diagnosis and clinical treatment as well as prognosis, thus providing a better understanding of C. kerstersii-related infections.

Fatal bacteremia caused by Staphylococcus argenteus: A case report.

RATIONALE: Staphylococcus argenteus (S argenteus) is a novel and emerging species that is part of the Staphylococcus aureus (S aureus) complex. Fatal cases of bloodstream infection caused by S argenteus are rarely reported and should be considered in medical practice. PATIENT CONCERNS: A 44-year-old male was admitted to our hospital with reduced appetite, high fever and unconsciousness. Laboratory tests indicated infection, muscle damage, and alkalosis in the patient. Brain computed tomography (CT) demonstrated small hematoma in left frontal lobe with peripheral cerebral edema. Chest CT demonstrating chronic bronchitis, emphysema, and bullae in the right lung. Blood culture was collected on the first day of hospitalization for microbial culture and pathological examination. DIAGNOSIS: The isolate from blood culture was identified as S argenteus by MALDI-TOF MS after the patient death. INTERVENTIONS: The patient was subjected to empirical antibiotic treatment with piperacillin/tazobactam. OUTCOMES: After 48 hours of hospitalization, the patient died after ineffective rescue. LESSONS: The patient had long-term heavy drinking and smoking as well as chronic malnutrition, which may account for his immune deficiency. The immunocompromised people are more vulnerable to infection by S argenteus and then develop bacteremia. The use of piperacillin/tazobactam may have contributed to the patient death.

Genomic characterization of Pantoea anthophila strain UI705 causing urinary tract infections in China.

Introduction: Pantoea anthophila (P. anthophila) is a Gram-negative bacterium initially isolated from Impatiens balsamina in India. P. anthophila has been characterized with low pathogenicity, and no human infections caused by this organism have been reported yet. We report the first case of urinary tract infection caused by P. anthophila in a 73-year-old man after bladder cancer surgery. Methods: The bacterial isolate gained from urine was named UI705 and identified as P. anthophila by MALDI-TOF mass spectrometry. The genome sequencing and analysis were performed to further characterize the pathogenesis of the clinical isolate. Result and discussion: To the best of our knowledge, this is the first report of human infection caused by P. anthophila in China. The draft genome sequence of P. anthophila UI705 provides a fundamental resource for subsequent investigation of its virulence factors, antibiotic resistance, host-pathogen interactions, and comparative genomics of genus Pantoea.

T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Association of elevated mid-pregnancy maternal plasma ferritin concentrations and triglyceride concentrations with the risk of gestational diabetes mellitus: A prospective cohort study.

OBJECTIVE: Ferritin levels are well known to be associated with gestational diabetes mellitus (GDM). However, the association of the combination of ferritin and triglyceride (TG) levels in early mid-pregnancy with GDM has not been studied in depth. We investigated the independent and combined relationships of plasma ferritin and TG concentrations with the risk of GDM as well as the mediation effect of TG on ferritin. METHODS: We analysed 2071 pregnant women from the Tongji Maternal and Child Health Cohort who had their plasma ferritin and TG concentrations measured at 11-20 weeks of gestation. Associations between ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Youden's index was calculated to find the cut-off values of ferritin and TG by ROC curve analysis. The mediation effect of the TG concentration on the ferritin level with GDM risk was explored by a mediation analysis. RESULTS: A total of 264 (12.3%) participants developed GDM. The median and IQR of ferritin was 53.9 (30.5-92.7) ng/mL. After adjusting for potential confounders, the relative risks (RRs) and 95% confidence intervals of GDM were 2.19 (1.42, 3.39) for ferritin and 2.02 (1.37, 2.97) for TG. The adjusted RR for combination was 2.40 (1.62, 3.55). Moreover, we found that the TG concentration mediated 15.0% of the total effect of the ferritin concentration on the risk of GDM. CONCLUSIONS: Women with a combination of both high plasma ferritin (˃55.7 ng/mL) and high TG (˃1.9 mmoL/L) were at the highest risk of GDM. Additionally, we have revealed for the first time that an elevated maternal TG concentration in early pregnancy mediates the relationship between ferritin concentration and GDM risk. TRIAL REGISTRATION: This trial is registered at https://ClinicalTrials.gov as NCT03099837.

LncRNA BCAR4 promotes migration, invasion, and chemo-resistance by inhibiting miR-644a in breast cancer.

BACKGROUND: Metastasis and drug resistance of breast cancer have become a barrier to treating patients successfully. Long noncoding RNAs (lncRNAs) are known as vital players in cancer development and progression.  METHODS: The RT-qPCR were used to detect the gene expression. Colony formation assay, would healing assay, and transwell assay were performed to investigate oncogenic functions of cells. CCK8 assay was used to detect the cell viability. Western blot was applied to detect the protein level. Dual-luciferase reporter assay was used to determine the relationship between molecules. Mouse orthotopic xenograft tumor models were established to evaluate the effects of BCAR4 on tumor growth and metastasis in vivo.  RESULTS: LncRNA BCAR4 was significantly increased in breast cancer patients' tissues and plasma and upregulated in breast cancer cell lines. BCAR4 upregulation was correlated with the TNM stages and decreased after surgical removal of breast tumors. Silencing of BCAR4 suppressed breast cancer cell colony formation, migration, invasion, and xenograft tumor growth and promoted chemo-sensitivity. Mechanistically, BCAR4 facilitates breast cancer migration and invasion via the miR-644a-CCR7 axis of the MAPK pathway. BCAR4 promotes ABCB1 expression indirectly by binding to and down-regulating miR-644a to induce chemo-resistance in breast cancer. CONCLUSIONS: Our findings provide insights into the oncogenic role of BCAR4 and implicate BCAR4 as a potential diagnostic biomarker and a promising therapeutic agent to suppress metastasis and inhibit chemo-resistance of breast cancer.

First case report of human infection with Micrococcus yunnanensis identified by 16S rRNA gene sequencing: A case report.

BACKGROUND: Micrococcus yunnanensis (M. yunnanensis) is an endophytic actinomycete that was originally isolated from the roots of Polyspora axillaris in 2009, and no human infections caused by this organism have yet been reported. We report the first case of community-acquired pneumonia caused by M. yunnanensis and propose that M. yunnanensis should be considered as an emerging pathogen in medical practice. A 30-year-old woman was admitted to our hospital with fever, paroxysmal dry cough with sputum, and pharyngalgia. Laboratory tests revealed an increase in several inflammatory indicators, and a computerized tomography scan of the chest showed scattered infection foci in both lungs. Bronchoalveolar lavage fluid was collected via bronchoscopy for microbial culture and pathological examination. METHODS: The isolate from bronchoalveolar lavage fluid was identified as M. yunnanensis by 16S rRNA gene sequencing. The patient was diagnosed with community-acquired pneumonia based on the diagnostic criteria. RESULTS: The patient was treated with intravenous amoxicillin/clavulanate potassium, levofloxacin hydrochloride tablets, and compound methoxyphenamine capsules on the day after admission. After 3 days of treatment, the patient's physiological conditions and inflammatory indicators normalized, and 6-month follow-up showed no abnormalities. CONCLUSION: Although the pathogenicity of M. yunnanensis is unclear, the present case indicates an emerging pathogen in medical practice. MALDI-TOF MS has a limited ability to identify novel or rare pathogenic species, and 16S rRNA gene sequencing is of great value in some circumstance.

Higher serum adrenomedullin concentration is associated with an increased risk of gestational diabetes mellitus: A nested case-control study in Wuhan, China.

Adrenomedullin (ADM) is thought to play a significant role in regulating insulin secretion and glucose metabolism. However, studies on the relationship between ADM and gestational diabetes mellitus (GDM) are limited. We hypothesized that a higher serum ADM concentration would be associated with an increased risk of GDM. Therefore, a nested case-control study of 65 GDM cases and 130 prepregnancy body mass index, age, parity, and gestational age of blood collection-matched controls was conducted to prospectively evaluate the association between circulating ADM concentrations in early pregnancy and the risk of GDM in pregnant women based on the Tongji Birth Cohort. Serum ADM concentrations in the GDM group were higher than those in the control group (2125.04 ± 644.97 vs 1880.76 ± 581.13 pg/mL) (P = .008). Serum ADM concentration was positively associated with the risk of developing GDM (Ptrend < .05). The adjusted odds ratio (OR) comparing the highest tertile of ADM with the lowest was 2.74 (95% CI, 1.17-6.43). The risk of GDM increased by 49% (OR, 1.49; 95% CI, 1.05-2.12) for each SD increment of serum ADM. Moreover, serum ADM concentration was positively correlated with circulating total cholesterol (r = 0.204), triglycerides (r = 0.197), and systolic blood pressure (r = 0.173), but negatively correlated with circulating high-density lipoprotein cholesterol concentration (r = -0.176). Pregnant women with higher serum ADM concentrations have a markedly increased risk of developing GDM. Further studies are warranted to explore the possible thresholds of ADM that increase the risk of GDM and to confirm and elucidate the underlying mechanisms.

Hemodialysis catheter-related infection caused by Pannonibacter phragmitetus: a rare case report in China.

Pannonibacter phragmitetus (P. phragmitetus) is rarely related with human disease. We reported a case of catheter-related infection caused by P. phragmitetus in a 68-year-old woman on hemodialysis. The patient developed recurrent fever during hemodialysis and blood cultures were positive for P. phragmitetus. The patient's body temperature returned to normal after intravenous cefoperazone/sulbactam treatment, and the hemodialysis catheter was locked with gentamicin and urokinase. The potential anti-infective treatment against P. phragmitetus was discussed.

Case report: Infective endocarditis caused by Streptococcus sinensis: The first case in mainland China and literature review.

Streptococcus sinensis was originally described as a causative agent for infective endocarditis in three Chinese patients from Hong Kong in 2002. Subsequently, several cases were reported outside Hong Kong, indicating that it is an emerging pathogen worldwide. We isolated a closely related strain in a young patient diagnosed with infective endocarditis in mainland China. In this paper, we reviewed the course of infection and provided a comprehensive comparison of its clinical characteristics with the reported cases.

Nipple adenoma with ipsilateral Spitz nevus in a 26-year-old female: a case report.

A 26-year-old female with a palpable mass and progressively darker itchy area in her left nipple was admitted to hospital. The left nipple surface showed furfuraceous desquamation and bloody discharge, with a 1.0×0.7×0.4 cm area of grayish-brown pigmentation in the ipsilateral nipple and areola. Surgical resection of the primary skin tumor and biopsy of the partial mass in the middle of the nipple were undertaken since color Doppler ultrasonography and dermoscopy were unable to make a differential diagnosis. We thus report the first case of a nipple adenoma with concomitant ipsilateral nipple areola Spitz nevus.

LINC00094/miR-19a-3p/CYP19A1 axis affects the sensitivity of ER positive breast cancer cells to Letrozole through EMT pathway.

The endocrine therapy resistance of breast cancer is the difficulty and challenge to be urgently solved in the current treatment. In this study, we examined the effects of noncoding RNA LINC00094 and miR-19a-3p on breast cancer in vivo and in vitro by RT-QPCR, Western Blot, luciferase assay, immunofluorescence and drug sensitivity tests. The plasma level of CYP19A1 in patients with breast cancer resistance was lower than that in drug sensitive patients. Compared with normal subjects, miR-19a-3p was highly expressed in plasma of patients with breast cancer. miR-19a-3p is highly expressed in estrogen receptor positive breast cancer cells. The expression of miR-19a-3p promoted the migration and EMT of breast cancer cells and reduced the sensitivity of breast cancer to Letrozole. LINC00094 sponge adsorbed miR-19a-3p. LINC00094 promotes the expression of CYP19A1, the target gene of miR-19a-3p, and inhibits the EMT process of breast cancer, ultimately promoting the sensitivity of ER-positive breast cancer cells to Letrozole. This study found a new mechanism of Letrozole sensitivity in ER positive breast cancer.

TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway.

Liver cancer is a malignant cancer phenotype for which there currently remains a lack of reliable biomarkers and therapeutic targets for disease management. Tryptophan 2,3­dioxygenase (TDO2), a heme­containing polyoxygenase enzyme, is primarily expressed in cells of the liver and nervous systems. In the present study, through the combination of cancer bioinformatics and analysis of clinical patient samples, it was shown that TDO2 expression in liver cancer tissue samples was significantly higher than that in normal tissues, and liver cancer patients with high TDO2 expression had a poor prognosis. Mechanistic studies on liver cancer cells showed that TDO2 promoted cancer cell migration and invasion via signal transduction through the Wnt5a pathway. Such regulation impacted the expression of cancer­associated biomarkers, such as matrix metalloprotease 7 (MMP7) and the cell adhesion receptor CD44. Treatment with a calcium channel blocker (azelnidipine) reduced TDO2 levels and inhibited liver cancer cell migration and invasion. A mouse xenograft cancer model showed that TDO2 promoted tumorigenesis. Furthermore, azelnidipine treatment to downregulate TDO2 also decreased liver cancer development in this mouse cancer model. TDO2 is thus not only a useful liver cancer biomarker but a potential drug target for management of liver cancer.

Association of maternal neutrophil count in early pregnancy with the development of gestational diabetes mellitus: a prospective cohort study in China.

OBJECTIVE: We evaluated the potential role of maternal serum levels of neutrophils in the first trimester of pregnancy in the prediction of gestational diabetes mellitus (GDM). METHODS: This prospective cohort study enrolled singleton pregnant women before gestational weeks 16 and evaluated them until delivery. Among the 1467 pregnant women who performed prenatal care before 14 weeks of gestation in the cohort, a total of 731 were eligible for the final analysis. The associations between neutrophil counts, white blood cell count, neutrophil to lymphocyte ratio, and GDM (assessed by a 75-g oral glucose tolerance test between 24 and 28 weeks) were evaluated by multivariate logistic regression. RESULTS: Neutrophil count outperformed the neutrophil to lymphocyte ratio and white blood cell count in predicting GDM occurrence. We applied a smoothing function and found that neutrophil count was associated with both fasting blood glucose (FBG) (p=.0149) and 1-h postprandial blood glucose (PBG) (p=.0187) after adjustment pre-pregnancy body mass index, family history of diabetes, and age. Logistic regression analysis found that the highest neutrophil count level (6.28-14.73 × 109/L) had a 1.85-fold (95% CI 1.10, 3.09) increased risk of GDM compared with that of the lowest tertile (1.47-4.82 × 109/L). CONCLUSIONS: The results indicated an association between higher neutrophil levels and GDM occurrence.