Comparative transcriptomics reveals common and strain-specific responses of human macrophages to infection with Mycobacterium tuberculosis and Mycobacterium bovis BCG.

Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (M. bovis) are closely related pathogenic mycobacteria known to cause chronic pulmonary infections in both humans and animals. Despite sharing nearly identical genomes and virulence factors, these two bacteria display variations in host tropism, epidemiology, and clinical presentations. M. bovis Bacillus Calmette-Guérin (BCG) is an attenuated strain of M. bovis commonly utilized as a vaccine for tuberculosis (TB). Nevertheless, the molecular underpinnings of these distinctions and the intricacies of host-pathogen interactions remain areas of ongoing research. In this study, a comparative transcriptomic analysis was conducted on human leukemia macrophages (THP-1) infected with either MTB H37Rv or M. bovis BCG (Tokyo strain) to elucidate common and strain-specific responses at the transcriptional level. RNA sequencing was utilized to characterize the transcriptomes of human primary macrophages infected with MTB or BCG at 6 and 24 h post-infection. The findings indicate that both MTB and BCG induce substantial and dynamic alterations in the transcriptomes of THP-1, with a notable overlap in the quantity and extent of differentially expressed genes (DEGs). Moreover, gene ontology (GO) enrichment analysis unveiled shared pathways related to immune response, cytokine signaling, and apoptosis. The immune response of macrophages to bacterial infections at 6 h exhibited significantly greater intensity compared to that at 24 h. Furthermore, distinct gene sets displaying notable variances between MTB and BCG infections were identified. The profound impact of MTB infection on macrophage gene expression, particularly within the initial 6 h, was evident. Additionally, downregulation of pathways such as Focal adhesion, Rap1 signaling pathway, and Regulation of actin cytoskeleton was observed. The pathways associated with inflammation reactions and cell apoptosis exhibited significant differences, with BCG triggering macrophage apoptosis and MTB enhancing the survival of intracellular bacteria. Our findings reveal that MTB and BCG provoke similar yet distinct transcriptional responses in human macrophages, indicating variations in their pathogenesis and ability to adapt to host environments. These results offer novel insights into the molecular mechanisms governing host-pathogen interactions and may contribute to a deeper understanding of TB pathogenesis.

Recent advances in aggregation-induced emission luminogens in photoacoustic imaging.

Photoacoustic imaging (PAI) is a rapidly emerging modality in biomedical research with the advantages of noncontact operation, high optical resolution, and deep penetration. Great efforts and progress in the development of PAI agents with improved imaging resolution and sensitivity have been made over the past 2 decades. Among them, organic agents are the most promising candidates for preclinical/clinical applications due to their outstanding in vivo properties and facile biofunctionalities. Motivated by the unique properties of aggregation-induced emission (AIE) luminogens (AIEgens), various optical probes have been developed for bioanalyte detection, multimodal bioimaging, photodynamic/photothermal therapy, and imaging-guided therapeutics. In particular, AIE-active contrast agents have been demonstrated in PAI applications with excellent performance in imaging resolution and tissue permeability in vivo. This paper presents a brief overview of recent progress in AIE-based agents in the field of photoacoustic imaging. In particular, we focus on the basic concepts, data sorting and comparison, developing trends, and perspectives of photoacoustic imaging. Through numerous typical examples, the way each system realizes the desired photoacoustic performance in various biomedical applications is clearly illustrated. We believe that AIE-based PAI agents would be promising multifunctional theranostic platforms in clinical fields and will facilitate significant advancements in this research topic.

Hotair mediates tumorigenesis through recruiting EZH2 in colorectal cancer.

Long noncoding RNAs (lncRNA)  have been demonstrated to extensively participate in a wide spectrum of biological activities ranging from embryogenesis and cancer progression. HOX transcript antisense RNA (Hotair), an lncRNA located in the HOXC locus, has been reported to play an important role in carcinogenesis. As a well-known oncogene, it potentiates cancer metastasis and tumor progression. And it also serves as a biomarker for poor prognosis and tumor recurrence. In this study, Hotair was found to be upregulated in colorectal cancer (CRC) cells and clinical specimens. Further investigation showed that knockdown of Hotair dramatically suppressed cell proliferation and colony formation, suggesting that Hotair may stimulate tumorigenesis of CRC. The enhancer of zeste homolog 2 (EZH2), a regulator of epigenetic modification, was upregulated in CRC cells and clinical samples. And the silence of EZH2 significantly suppressed cell viability and colony formation. Furthermore, the RNA immunoprecipitation assay revealed that Hotair directly bound EZH2 in CRC cells. In conclusion, Hotair mediated tumorigenesis via recruiting EZH2, which might shed light on the development of a novel therapeutic approach for patients with CRC.

Huge gastric plexiform fibromyxoma presenting as pyemia by rupture of tumor: A case report.

BACKGROUND: Plexiform fibromyxoma (PF) is a rare mesenchymal tumor, with limited case reports worldwide. Common clinical symptoms are abdominal discomfort and bleeding signs, which frequently present slow-onset in reported cases. Herein, we report a case of gastric PF presenting as acute onset and with pyemia accom-panying tumor rupture. We resected the tumor as well as the distal gastric, bulbus duodeni and gallbladder for treatment in emergency surgery. Notably, before the onset of the disease, the patient received coronavirus disease 2019 (COVID-19) vaccines. CASE SUMMARY: A 26-year-old man was admitted to our hospital, due to abdominal pain and fever after having received COVID-19 vaccines. Laboratory examination indicated severe sepsis. Computed tomography scan revealed a large mass in the abdomen. Deformation of the gastrointestinal tract was seen during gastroscopy. After failure of anti-infective treatment and symptoms of shock developed, he received an emergency surgery. We found a huge and partly ruptured mass, with thick purulence. Microscopically, the mass was composed of spindle cells with clarified cytoplasm, accompanied by myxoid stroma and arborizing blood vessels. Immunohistochemistry showed the tumor cells as positive for smooth muscle actin and succinate dehydrogenase subunit B but negative for DOG-1 and CD117. Finally, the patient was diagnosed with gastric PF and discharged from the hospital. CONCLUSION: Gastric PF manifesting as tumor rupture combined with pyemia is rare. Timely surgery is critical for optimal prognosis.

BAG2 Overexpression Correlates with Growth and Poor Prognosis of Esophageal Squamous Cell Carcinoma.

Previous studies have suggested that Bcl2-associated athanogene 2 (BAG2) serves as a crucial regulator for tumorigenesis in multiple tumors. However, little is known about the effect of BAG2 on esophageal squamous cell carcinoma (ESCC). This study focused on investigating whether BAG2 functions as a cancer-promoting gene in ESCC. In this work, gene expression data and clinical information from the NCBI Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) were collected and analyzed. Expression of BAG2 in ESCC was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). BAG2 was knocked down using small interference RNA (si-RNA) approach. Cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8) and transwell assays. Molecular mechanism was detected by western blotting assay. The expression of BAG2 both in ESCC tissues and cells was upregulated and overexpression was associated with worsened prognosis. BAG2 silencing inhibited ESCC cell proliferation, migration and invasion, which was regulated by the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. These results reveal contributions of BAG2 as a predictor and potential therapeutic target in ESCC.

[Application of hyperthermic intraoperative intraperitoneal chemotherapy in patients with gastric cancer].

OBJECTIVE: To explore the effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) on the postoperative metastatic rate and survival rate of advanced gastric cancer (AGC). METHODS: In HIIC group, patients received HIIC (mitomycin C 30 mg and cisplatin 100 mg were added into 2000 ml distilled water, heated to 42 approximately 45 degrees C, perfused to abdominal cavity for 30 min and then sucked) and intravenous chemotherapy after operation (5- FU 10 approximately 15 mg/kg, mitomycin C 0.1 approximately 0.15 mg/kg, adriamycin 0.5 approximately 1 mg/kg i.v drip, once a week for 2 approximately 3 weeks). In control group, patients received intravenous chemotherapy only. The postoperative metastatic rate and survival rate (1- , 3- and 5- year) of patients were compared between 92 cases of AGC undergone HIIC and 120 cases of AGC without HIIC (control group). RESULTS: The peritoneal recurrence rates after operations occurred within two years were 14.1% and 37.5% in HIIC group and control group respectively (P < 0.01). The 1- , 3- , and 5- year survival rates in HIIC group were 98.9%, 68.5%, and 52.2% and in control group 95.0%, 56.7% and 37.5% respectively. The 3- , and 5- year survival rates were significantly different between the two the groups (P < 0.05). CONCLUSION: HIIC can kill isolated intraperitoneal cancer cells, reduce peritoneal recurrence rate after operations, raise significantly survival rate of patient, and improve the prognosis of AGC.

[Diagnosis and treatment of mesenteric venous thrombosis early after operation].

OBJECTIVE: To analyze the clinical characteristics diagnosis and treatment of patients with mesenteric venous thrombosis early after operation. METHODS: A retrospective study was performed on the clinical data of 7 patients with mesenteric venous thrombosis early after operation from 1990 to 2004. RESULTS: Patients had main clinical manifestations of severe abdominal pain and vomiting, but abdominal signs were slight. The systemic toxic symptoms occurred in 2 cases at late course. The examination of abdominal X- ray showed intestinal obstruction of all patients. Four patients received abdominal CT- scanning, of whom 3 patients were diagnosed as mesenteric venous thrombosis. Seven patients received exploratory operation. The necrotic intestinal segments were resected. Two patients had short intestinal syndromes after operation, one of them died of serious malnutrition. Four patients who had recurrence of portal, mesenteric and iliac venous thrombosis needed a long-term therapy of warfarin and aspirin after discharge. CONCLUSION: It is easy to make a mistake in diagnosis because of the lacking of characteristic clinical manifestations. Exploratory operation immediately plus anticoagulant therapy is strongly recommended.

[Effect of diode laser coagulation treatment on grade III internal hemorrhoids].

OBJECTIVE: To evaluate the curative effects of diode laser coagulation on grade III internal hemorrhoids. METHODS: From March 2004 to December 2004, 86 patients with grade III internal hemorrhoids were divided into two groups, received laser coagulation (laser group, n=46) or received hemorrhoidectomy (control group, n=40). Complications, symptom relief, pain scores and satisfaction scores were compared between the two groups six months after operation. RESULTS: Pain scores were lower in laser group than that of the control group on the first day and seventh day after operation. Small amount of bleeding occurred in the laser group (12 cases) and control group (35 cases), however, non of them required special hemostasis. Laser coagulation and closed hemorrhoidectomy were equally effective in controlling symptomatic prolapse. There was no difference in terms of continence scores and patients satisfaction between the two groups (P> 0.05). CONCLUSIONS: Diode laser coagulation can be considered as a safe and effective procedure for the treatment of grade III hemorrhoids.