Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis.

INTRODUCTION: Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. METHODS: Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. RESULTS: Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26-42%] in 2021 to 25% [19-34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63-86%] to 58% [47-74%], but incidence remained 4.3-fold [3.3-5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7-7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6-7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9-3.4] in 2071. CONCLUSIONS: Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

Pediatric upper lip myopericytoma: a case report and comprehensive review.

BACKGROUND: Myopericytoma is a rare spindle cell tumor of mesenchymal origin, typically benign, characterized by concentric proliferation of tumor cells around blood vessels within subcutaneous tissue. It primarily occurs in middle-aged adults and is often located in distal extremities, although cases have been reported in proximal extremities and head-neck regions. However, occurrences within the oral cavity are exceedingly rare. To date, literature reviews have identified only two cases in children under 10 years old and reported only five cases of myopericytoma occurring in the lip region. We provide a comprehensive review and analysis of all documented cases to better understand this condition. CASE PRESENTATION: A 7-year-old girl presented to oral and maxillofacial surgery with the discovery of a painless mass on the inner aspect of the upper lip. The diagnosis of myopericytoma was confirmed by histological examination (HE staining), alcian blue staining, and immunohistochemistry. CONCLUSIONS: Following surgical excision, there were no signs of recurrence at a 3-month follow-up. The pathological diagnosis of myopericytoma is quite challenging, and immunohistochemical testing is necessary.

Potential Benefits of Green Tea in Prostate Cancer Prevention and Treatment: A Comprehensive Review.

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.

Successful Outcome of a Patient with Concomitant Pancreatic and Renal Carcinoma Receiving Secoisolariciresinol Diglucoside Therapy Alone: A Case Report.

Introduction: Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment. Patient Concerns: We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy. Diagnosis: Pancreatic and kidney cancers. Interventions: We gave dietary SDG to the patient as the only therapeutics. Outcomes: SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far. Conclusion: These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors.

Development and Characterization of an Antioxidant and Antimicrobial Film Composited by Hydroxyethyl Cellulose and Sulfated Rice Bran Polysaccharides for Food Packaging.

The nonantimicrobial properties and relatively poor mechanical properties of hydroxyethyl cellulose (HEC) limit its use in packaging. Sulfated rice bran polysaccharides (SRBP) possess significant antioxidant and antimicrobial activities. The purpose of this study was to investigate the effect of different concentrations of SRBP on the physical and mechanical properties and the functional characteristics of HEC/SRBP films. The physical properties of the HEC/20% SRBP films, such as water resistance, water vapor barrier, light barrier, and tensile strength, improved significantly (p < 0.05) compared with those of the HEC films. Scanning electron microscopy and Fourier transform infrared spectrometry showed that HEC formed hydrogen bonds with SRBP and exhibited better compatibility. Thermogravimetric analysis revealed that the addition of SRBP was beneficial to the thermal stability of the films. In addition, the antioxidant and bacteriostatic properties of the films were enhanced by the addition of SRBP to HEC, with the 20% SRBP films showing the most significant enhancement in activity. Therefore, the HEC/20% SRBP films show potential for development for use as active food packaging.

Mechanisms and markers of malignant transformation of oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic premalignant disease associated with betel quid chewing. Epidemiological studies indicate that there are approximately 5 million individuals suffering from OSF worldwide, with a concerning malignancy transformation rate of up to 4.2 %. When OSF progresses to oral squamous cell carcinoma (OSCC), the 5-year survival rate for OSCC drops to below 60 %. Therefore, early screening and diagnosis are essential for both preventing and effectively treating OSF and its potential malignant transformation. Numerous studies have shown that the malignant transformation of OSF is associated with various factors, including epigenetic reprogramming, epithelial-mesenchymal transition, hypoxia, cell cycle changes, immune regulation disturbances, and oxidative damage. This review article focuses on the unraveling the potential mechanisms underlying the malignant transformation of OSF, as well as the abnormal expression of biomarkers throughout this transformative process, with the aim of aiding early screening for carcinogenic changes in OSF. Furthermore, we discuss the significance of utilizing blood and saliva components from patients with OSF, along with optical diagnostic techniques, in the early screening of OSF malignant transformation.

miR-30a-5p targets ITGA6 to inhibit oral squamous cell carcinoma progression.

OBJECTIVE: Nowadays, many studies focus on the relationship between microRNAs (miRs) and the development of oral squamous cell carcinoma (OSCC). Here, we broaden the understanding of miR-30a-5p in OSCC. METHODS: In silico analysis was implemented to screen differentially expressed genes in OSCC and the related upstream regulatory miR. OSCC SCC9 cells were manipulated with lentivirus-mediated miR-30a-5p mimic, oe-ITGA6 or sh-ITGA6 and LY294002 (the PI3K/AKT pathway inhibitor) for studying their roles in cell biological processes. Tumors were xenografted in nude mouse for in vivo mechanism verification. RESULTS: In silico analysis results depicted that ITGA6 was highly expressed in OSCC, and that miR-30a-5p was the upstream regulatory miR of ITGA6. miR-30a-5p was downregulated and ITGA6 was highly expressed in OSCC tissues and cells. miR-30a-5p targeted and downregulated ITGA6. ITGA6 promoted epithelial-mesenchymal transition, migration and invasion in OSCC cells by activating PI3K/AKT pathway. miR-30a-5p could suppress the in vivo growth and metastasis of OSCC by inhibiting the ITGA6/PI3K/AKT axis. CONCLUSION: Taken together, miR-30a-5p prevents OSCC progression by inhibiting PI3K/AKT pathway through inhibition of ITGA6 expression.

[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Evaluation of bronchoscopic direct vision glottis anesthesia method in bronchoscopy.

BACKGROUND: Fibrobronchoscopy is a common adjunct tool that requires anesthesia and is widely used in the diagnosis and treatment of various respiratory diseases. However, current anesthesia methods, such as spray, nebulized inhalation, and cricothyroid membrane puncture, have their own advantages and disadvantages. Recently, studies have shown that bronchoscopic direct-view glottis anesthesia is a simple and inexpensive method that shortens the examination time and provides excellent anesthetic results. AIM: To evaluate the effectiveness of bronchoscopic direct vision glottis anesthesia for bronchoscopy. METHODS: The study included 100 patients who underwent bronchoscopy during thoracic surgery. A random number table method was used to divide the patients into control and observation groups (50 patients each). The control and observation groups were anesthetized using the nebulized inhalation and bronchoscopic direct vision glottis method, respectively. Hemodynamic indices [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and oxygen saturation (SpO2) before (T1), 5 min after anesthesia (T2), and at the end of the operation (T3)] serum stress hormone indices [norepinephrine (NE), epinephrine (E), adrenocorticotropic hormone (ACTH), and cortisol (Cor) before and after treatment] were compared between the 2 groups. Adverse effects were also compared between the two groups. RESULTS: At T2 and T3, SBP, DBP, and HR were lower in the observation group than the control group, whereas SpO2 was higher than the control group [(119.05 ± 8.01) mmHg vs (127.05 ± 7.83) mmHg, (119.35 ± 6.66) mmHg vs (128.39 ± 6.56) mmHg, (84.68 ± 6.04) mmHg vs (92.42 ± 5.57) mmHg, (84.53 ± 4.97) mmHg compared to (92.57 ± 6.02) mmHg, (74.25 ± 5.18) beats/min compared to (88.32 ± 5.72) beats/min, (74.38 ± 5.31) beats/min compared to (88.42 ± 5.69) beats/min, (97.36 ± 2.21)% vs (94.35 ± 2.16)%, (97.42 ± 2.36)% vs (94.38 ± 2.69%], with statistically significant differences (all P < 0.05). After treatment, NE, E, ACTH, and Cor were significantly higher in both groups than before treatment, but were lower in the observation group than in the control group [(68.25 ± 8.87) ng/mL vs (93.35 ± 14.00) ng/mL, (53.59 ± 5.89) ng/mL vs (82.32 ± 10.70) ng/mL, (14.32 ± 1.58) pg/mL vs (20.35 ± 3.05) pg/mL, (227.35 ± 25.01) nmol/L vs (322.28 ± 45.12) nmol/L], with statistically significant differences (all P < 0.05). The incidence of adverse reactions was higher in the control group than in the observation group [12.00% (12/50) vs 6.00% (3/50)] (P < 0.05). CONCLUSION: The use of bronchoscopic direct vision glottis anesthesia method for bronchoscopy patients is beneficial for stabilizing hemodynamic indices during bronchoscopy and reducing the level of patient stress, with good safety and practicality.

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

Ghrelin promotes cardiomyocyte differentiation of adipose tissue­derived mesenchymal stem cells by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.

Adipose tissue­derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric­secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription­quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and ß­catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration­dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α­myosin heavy chain (α­MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased ß­catenin accumulation in nucleus and decreased the protein expression of secreted frizzled­related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation­associated terms and Wnt pathways. Dead­box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac­specific markers and ß­catenin and enhanced the fluorescence intensity of α­MHC and ß­catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin­enhanced protein levels of cardiac­specific markers and the fluorescence intensity of α­MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Safety and efficacy of percutaneous electrocoagulation haemostasis in the treatment of grade IV haemorrhagic cystitis after allogeneic haematopoietic stem cell transplantation in children: a retrospective analysis.

BACKGROUND: To investigate the efficacy and safety of endoscopic electrocoagulation haemostasis via a percutaneous transhepatic approach for the treatment of grade IV haemorrhagic cystitis (HC) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 14 children with severe HC, who were admitted to Hebei Yanda Hospital between July 2017 and January 2020, were analysed retrospectively. There were nine males and five females, with an average age of 8.6 years (range: 3 to 13 years). After an average of 39.6 (7 to 96) days of conservative treatment in the hospital's haematology department, the bladders of all patients were filled with blood clots. A small 2-cm incision was made in the suprapubic area to enter the bladder and quickly clear the blood clots, and a percutaneous transhepatic approach to electrocoagulation and haemostasis was performed. RESULTS: In the 14 children, a total of 16 operations were performed, with an average operation time of 97.1 (31 to 150) min, an average blood clot of 128.1 (80 to 460) mL and an average intraoperative blood loss of 31.9 (20 to 50) mL. There were three cases of postoperative bladder spasm remission after conservative treatment. During the follow-up period of 1 to 31 months, one patient improved after one operation, 11 patients were cured after one operation, and two patients were cured after recurrent haemostasis by secondary electrocoagulation, four of whom died of postoperative non-surgical blood-related diseases and severe lung infections. CONCLUSION: Percutaneous electrocoagulation haemostasis can quickly remove blood clots in the bladders of children after allo-HSCT with grade IV HC. It is a safe and effective minimally invasive treatment.

A rare case of pemphigus vulgaris disguised as a malignant gingival ulcer.

BACKGROUND: Pemphigus vulgaris (PV) is a kind of rare and severe autoimmune bullous disease. In this case, the specificity of oral PV lies in the clinical manifestations of a single palatal ulcer, and no blisters were found in the oral mucosa. This case provides a powerful reference for dentists diagnosing and treating oral PV with atypical clinical presentations. CASE PRESENTATION: A 54 years old female patient presented with a non-healing palatal gingival ulcer for over three months. By histopathological H&E staining and the direct immunofluorescence (DIF) test, the final diagnosis was oral PV. After topical glucocorticoid therapy, the affected area was cured. CONCLUSIONS: In patients with prolonged erosion of the skin or oral mucosa, even if complete blisters are not visible, the physician should consider autoimmune bullous diseases and pay attention to avoid diagnostic defects.

LNX2 involves in the role of ghrelin to promote the neuronal differentiation of adipose tissue-derived mesenchymal stem cells.

Adipose tissue-derived mesenchymal stem cells (ADSCs) have promising effects on nerve repair due to the differentiation ability to neural cells. Ghrelin has been shown to promote the neural differentiation of ADSCs. This work was designed to explore its underlying mechanism. Herein, we found high expression of LNX2 in ADSCs after neuronal differentiation. Knockdown of LNX2 might block neuronal differentiation of ADSCs, as evidenced by the decreased number of neural-like cells and dendrites per cell, and the reduced expressions of neural markers (including ß-Tubulin III, Nestin, and MAP2). We also demonstrated that LNX2 silencing suppressed the nuclear translocation of ß-catenin in differentiated ADSCs. Luciferase reporter assay indicated that LNX2 inhibited wnt/ß-catenin pathway by reducing its transcriptional activity. In addition, results showed that LNX2 expression was increased by ghrelin, and its inhibition diminished the effects of ghrelin on neuronal differentiation. Altogether, the results suggest that LNX2 is involved in the role of ghrelin to facilitate neuronal differentiation of ADSCs.

Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses.

Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8+ T and CD49b+ NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3+ Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.

Active kisspeptin DNA vaccines oral immunization disrupt mRNA hormone receptors expression in ram lambs.

To evaluate the efficacy of oral immunization with active kisspeptin DNA vaccine on the expression of hormone receptor mRNA. For this study, ten 56-day-old Hu breed ram lambs were randomly assigned to the treatment and control groups (n = 5). Treatment Experimental group received C500/pKS-asd and the control group received C500/pVAX-asd (aspartate-ß semialdehyde dehydrogenase orally on days 0, 28, and 56, and blood samples were taken at each immunization interval (14-day) and tissues samples were collected at the end of the experimental period (day 98). The collected samples were stored in the refrigerator at -20 °C and liquid nitrogen, respectively, for laboratory examination. Total RNA was extracted from samples using TRIzol reagent and quantitative real-time polymerase chain reaction (QPCR) was used to quantify the levels of KISS1, G protein-coupled receptor-54 (Kiss1r), and gonadotrophin-releasing hormone (GnRH) mRNA in the hypothalamus. Levels of luteinizing hormone receptor (LHR) and luteinizing hormone beta (LHß) mRNA, and follicle-stimulating hormone receptor (FSHR) and follicle-stimulating hormone beta (FSHß) mRNA in the testes and pituitary were analyzed, respectively. Further, gonadotropin-releasing hormone receptor (GnRHR) mRNA expression level in the pituitary was measured. Moreover, the Kiss1r concentration level in the blood was measured using an indirect ELISA. The concentration of Kiss1r in the blood was lower in the treatment group than in the control group (p < 0.05). The levels of testicular FSHR and LHR mRNA were significantly lower in the treatment group (p < 0.05) when compared to the control group. Furthermore, the treatment group's levels of hypothalamic KISS1, Kiss1r, and GnRH mRNA were significantly lower (p < 0.05) than the controls. LH, FSH, and GnRHR mRNA expression in the pituitary were also significantly lower in the treatment group (p < 0.01 and p < 0.05, respectively). These findings imply that oral immunization with active kisspeptin DNA vaccine suppresses hormone receptor mRNA expression in the ram lambs.

POSTHEMORRHAGIC SHOCK MESENTERIC LYMPH IMPAIRS SPLENIC DENDRITIC CELL FUNCTION IN MICE.

ABSTRACT: Dendritic cell (DC)-mediated immune dysfunction is involved in the process of severe hemorrhagic shock that leads to sepsis. Although post-hemorrhagic shock mesenteric lymph (PHSML) induces immune organs injuries and apoptosis, whether PHSML exerts adverse effects on splenic DCs remains unknown. In this study, we established a hemorrhagic shock model (40 ± 2 mm Hg for 60 min) followed by fluid resuscitation with the shed blood and equal Ringer's solution and drained the PHSML after resuscitation. At 3 h after resuscitation, we harvested the splenic tissue to isolate DCs using anti-CD11c immunomagnetic beads and then detected the necrotic and apoptotic rates in splenocytes and splenic DCs. We also detected the levels of TNF-α, IL-10, and IL-12 in the culture supernatants and surface marker expressions of MHC-II, CD80, and CD86 of splenic DCs following LPS stimulation for 24 h. Second, we purified the DCs from splenocytes of normal mice to investigate the effects of PHSML treatment on cytokine production and surface marker expression following LPS stimulation. The results showed that PHSML drainage attenuated LPS-induced cell death of splenocytes and DCs. Meanwhile, PHSML drainage enhanced the DC percentage in splenocytes and increased the TNF-α and IL-12 production by DCs and the expressions of CD80, CD86, and MHCII of DCs treated by LPS. Furthermore, PHSML treatment reduced the productions of TNF-α, IL-10, and IL-12 and the expressions of CD80 and CD86 in normal DCs after treatment with LPS. In summary, the current investigation demonstrated that PHSML inhibited the cytokine production and surface marker expressions of DCs stimulated by LPS, suggesting that PHSML plays an important role in hemorrhagic shock-induced immunosuppression through the impairment of DC function and maturation.

Preoperative prediction of lymphovascular invasion in patients with T1 breast invasive ductal carcinoma based on radiomics nomogram using grayscale ultrasound.

Purpose: The aim of this study was to develop a radiomics nomogram based on grayscale ultrasound (US) for preoperatively predicting Lymphovascular invasion (LVI) in patients with pathologically confirmed T1 (pT1) breast invasive ductal carcinoma (IDC). Methods: One hundred and ninety-two patients with pT1 IDC between September 2020 and August 2022 were analyzed retrospectively. Study population was randomly divided in a 7: 3 ratio into a training dataset of 134 patients (37 patients with LVI-positive) and a validation dataset of 58 patients (19 patients with LVI-positive). Clinical information and conventional US (CUS) features (called clinic_CUS features) were recorded and evaluated to predict LVI. In the training dataset, independent predictors of clinic_CUS features were obtained by univariate and multivariate logistic regression analyses and incorporated into a clinic_CUS prediction model. In addition, radiomics features were extracted from the grayscale US images, and the radiomics score (Radscore) was constructed after radiomics feature selection. Subsequent multivariate logistic regression analysis was also performed for Radscore and the independent predictors of clinic_CUS features, and a radiomics nomogram was developed. The performance of the nomogram model was evaluated via its discrimination, calibration, and clinical usefulness. Results: The US reported axillary lymph node metastasis (LNM) (US_LNM) status and tumor margin were determined as independent risk factors, which were combined for the construction of clinic_CUS prediction model for LVI in pT1 IDC. Moreover, tumor margin, US_LNM status and Radscore were independent predictors, incorporated as the radiomics nomogram model, which achieved a superior discrimination to the clinic_CUS model in the training dataset (AUC: 0.849 vs. 0.747; P < 0.001) and validation dataset (AUC: 0.854 vs. 0.713; P = 0.001). Calibration curve for the radiomic nomogram showed good concordance between predicted and actual probability. Furthermore, decision curve analysis (DCA) confirmed that the radiomics nomogram had higher clinical net benefit than the clinic_CUS model. Conclusion: The US-based radiomics nomogram, incorporating tumor margin, US_LNM status and Radscore, showed a satisfactory preoperative prediction of LVI in pT1 IDC patients.