PD-1 inhibitor combined with Docetaxel exerts synergistic anti-prostate cancer effect in mice by down-regulating the expression of PI3K/AKT/NFKB-P65/PD-L1 signaling pathway.

BACKGROUND: Docetaxel is a yew compound antitumor agent with accurate antitumor efficacy, but its application is limited due to the high and serious adverse effects, and finding effective combination therapy options is a viable strategy. Immune checkpoint inhibitors have become hotspots in enhancing anti-tumor immunity by blocking immune checkpoint signaling pathways, but their response rate to monotherapy use is not high and the efficacy is minimal. OBJECTIVE: To explore the anti-tumor effects and mechanisms of the combination of PD-1 inhibitors and Docetaxel through in vivo experiments and develop a feasible combination treatment for the therapy of prostate cancer. METHODS: Tumor-bearing mice were subcutaneously injected with 0.1 ml RM-1 cells. Treatment were taken when the tumor growed up to 3 mm, after which the tumor and spleen were removed to test the antitumor effect with Flow cytometric (FACS) analysis, Immunohistochemistry, Western Blot. RESULTS: In this experiment, we found that PD-1 inhibitors combined with Docetaxel had a synergistic effect on mouse prostate cancer, inhibited the growth of prostate cancer, improved survival and reduced adverse reactions, increased spleen and tumor infiltrative CD4+ and CD8+ T cells, especially in group combination with low-dose Docetaxel, and were related to the PI3K/AKT/NFKB-P65/PD-L1 signaling pathway. CONCLUSION: Our study confirms that PD-1 inhibitors in combination with Docetaxel are a viable combination strategy and provide a safe and effective combination option for the clinical treatment of prostate cancer.

Effects of Medium Additives on the Mycelial Growth and Polysaccharide Biosynthesis in Submerged Culture of Bjerkandera fumosa.

Medium additives have been shown to affect the synthesis of active products in fungi. This study investigated the effects of corn stalk, poplar sawdust, Tween-80, and oleic acid on mycelial biomass and physicochemical properties, as well as the bioactivity of polysaccharides, including exopolysaccharides (EPS) and intracellular polysaccharides (IPS), in the submerged culture of Bjerkandera fumosa. Results showed that the addition of corn stalk or poplar sawdust increased the production of EPS but decreased the production of IPS; Tween-80 had less effect on the production of EPS and IPS; and oleic acid stimulated polysaccharide production significantly. Polysaccharide property analysis showed that the addition of corn stalk or poplar sawdust promoted the production of high-molecular-weight components in polysaccharides and changed the monosaccharide composition of polysaccharides, as well as increased the mannose, glucuronic acid, and xylose contents of IPS. Tween-80 and oleic acid also changed the molecular weight distribution of polysaccharides but only slightly affected the composition of monosaccharides. The bioactivity assay indicated that the polysaccharides obtained by adding corn stalk possessed high hydroxyl radical scavenging and antitumor activities. The effect of poplar sawdust was slightly weaker than that of corn stalk. EPS and IPS obtained from a culture with Tween-80 and oleic acid possessed low antioxidant activity. Moreover, their antitumor activity was improved and lost, respectively. The results obtained in this work are useful for improving the understanding of the optimization and regulation of bioactive polysaccharide production in the submerged culture of B. fumosa.

Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.

A particular GTPase-activating protein called RACGAP1 is involved in apoptosis, proliferation, invasion, metastasis, and drug resistance in a variety of malignancies. Nevertheless, the role of RACGAP1 in pan-cancer was less studied, and its value of the expression and prognostic of nasopharyngeal carcinoma (NPC) has not been explored. Hence, the goal of this study was to investigate the oncogenic and immunological roles of RACGAP1 in various cancers and its potential value in NPC. We comprehensively analyzed RACGAP1 expression, prognostic value, function, methylation levels, relationship with immune cells, immune infiltration, and immunotherapy response in pan-cancer utilizing multiple databases. The results discovered that RACGAP1 expression was elevated in most cancers and suggested poor prognosis, which could be related to the involvement of RACGAP1 in various cancer-related pathways such as the cell cycle and correlated with RACGAP1 methylation levels, immune cell infiltration and reaction to immunotherapy, and chemoresistance. RACGAP1 could inhibit anti-tumor immunity and immunotherapy responses by fostering immune cell infiltration and cytotoxic T lymphocyte dysfunction. Significantly, we validated that RACGAP1 mRNA and protein were highly expressed in NPC. The Gene Expression Omnibus database revealed that elevated RACGAP1 expression was associated with shorter PFS in patients with NPC, and RACGAP1 potentially influenced cell cycle progression, DNA replication, metabolism, and immune-related pathways, resulting in the recurrence and metastasis of NPC. This study indicated that RACGAP1 could be a potential biomarker in pan-cancer and NPC.

Study on the Antioxidant Effect of Shikonin-Loaded ß-Cyclodextrin Forming Host-Guest Complexes That Prevent Skin from Photoaging.

When the skin is overexposed to ultraviolet rays, free radicals will accumulate in the skin, causing lipid damage and even inducing photoaging of the skin. Combination therapy with antioxidant drugs is a good choice for topical treatment of skin photoaging due to its special physiological structure. In this paper, shikonin was encapsulated in ß-cyclodextrin (SH-ß-CD) by the precipitation crystallization method, which delayed the release of the drug and increased drug solubility. The average diameter of SH-ß-CD was 203.0 ± 21.27 nm with a zeta potential of -14.4 ± 0.5 mV. The encapsulation efficiency (EE%) was 65.9 ± 7.13%. The results of the in vitro permeation across the dialysis membrane and ex vivo transdermal release rates were 52.98 ± 1.21% and 88.25 ± 3.26%, respectively. In vitro antioxidant and antilipid peroxidation model assay revealed the antioxidant potential of SH and SH-ß-CD. In the mice model of skin photoaging, SH and SH-ß-CD had a recovery effect on the skin damage of mice, which could significantly increase the superoxide dismutase (SOD) activity in the skin. Briefly, SH-ß-CD had an obvious therapeutic effect on the skin photoaging of mice caused by UV, and it is promising in skin disease treatment and skin care.

Advances in bio-immunotherapy for castration-resistant prostate cancer.

Prostate cancer is one of the significant diseases that threaten the survival of men worldwide, with the progression of androgen deprivation therapy, become much rely on it, finally, developed into castration-resistant prostate cancer (ADT). In western countries, ranks second in incidence, and in China, with increasing lifespan, the incidence of prostate cancer is rising steadily. Although chemotherapy agents, such as taxane, have achieved some efficacy, treatment failure still occur. As sensitivity of hormone levels change, the disease can progress to castrate-resistant prostate cancer. Because of the poor efficacy of traditional surgery, endocrine therapy, radiation therapy, and chemotherapy, the treatment options for castrate-resistant prostate cancer are limited. Advanced prostate cancer can progress on immunotherapy, and thus, bio -immunotherapy targeting the unique, prostate microenvironment is an important option. In this paper, we systematically revealed the role of three types of bio-immunotherapies (immune checkpoint inhibitors, tumors, vaccines, cytokines) in castrate-resistant prostate cancer, providing a reference for clinical treatment of prostate cancer.

Identification of upregulated exosomal miRNAs between A2780 and A2780/DDP human ovarian cancer cells by high-throughput sequencing.

Exosomal miRNAs are known to play important roles in ovarian cancer and chemotherapeutic resistance. However, a systematic evaluation of characteristics of exosomal miRNAs involved in cisplatin resistance in ovarian cancer remains totally unclear. Exosomes (Exo-A2780, Exo-A2780/DDP) were extracted from cisplatin-sensitive cells (A2780) and cisplatin-resistant cells (A2780/DDP). Differential exosomal miRNA expression profiles were found by high-throughput sequencing (HTS). Target genes of the exo-miRNAs were predicted by using two online databases to increase the prediction accuracy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to find biological relationships with chemoresistance. RT‒qPCR of three exosomal miRNAs was performed, and a protein‒protein interaction (PPI) network was established to identify the hub genes. The GDSC database was used to prove the association between hsa-miR-675-3p expression and the IC50 value. An integrated miRNA-mRNA network was constructed to predict miRNA-mRNA associations. The connection between hsa-miR-675-3p and ovarian cancer was discovered by immune microenvironment analyses. The upregulated exosomal miRNAs could regulate gene targets through signalling pathways such as the Ras, PI3K/Akt, Wnt, and ErbB pathways. GO and KEGG analyses indicated that the target genes were involved in protein binding, transcription regulator activity and DNA binding. The RT‒qPCR results were consistent with the HTS data, and the results of PPI network analysis suggested that FMR1 and CD86 were the hub genes. GDSC database analysis and construction of the integrated miRNA-mRNA network suggested that hsa-miR-675-3p was associated with drug resistance. Immune microenvironment analyses showed that hsa-miR-675-3p was crucial in ovarian cancer. The study suggested that exosomal hsa-miR-675-3p is a potential target for treating ovarian cancer and overcoming cisplatin resistance.

Autophagy-related gene PXN as a prognostic marker: Promotion of ovarian cancer progression by suppressing the p110ß/Vps34/Beclin1 pathway.

Among gynecological malignancies, ovarian cancer has the highest mortality rate and has sparked widespread interest in studying the mechanisms underlying ovarian cancer development. Based on TCGA and GEO databases, we investigated the highly expressed autophagy-related genes that determine patient prognosis using limma differential expression and Kaplan-Meier survival analyses. The biological processes associated with these genes were also predicted using GO/KEGG functional enrichment analysis. CCK-8, cell scratch, and transwell assays were used to investigate the effects of PXN on the proliferation, migration, and invasion abilities of ovarian cancer cells. Transmission electron microscopy was used to observe the autophagosomes. The expression of autophagy proteins and the PI3K/Akt/mTOR and p110ß/Vps34/Beclin1 pathway proteins in ovarian cancer cells was detected using western blot; autophagy protein expression was further detected and localized using cellular immunofluorescence. A total of 724 autophagy-related genes were found to be overexpressed in ovarian -cancer tissues, with high expression of PEX3, PXN, and RB1 associated with poor prognosis in patients (p < .05). PXN activates and regulates signaling pathways related to cellular autophagy, ubiquitination, lysosomes, PI3K-Akt, and mTOR. Autophagosomes were observed in all cell groups. The increase in PXN gene expression promoted the proliferation, migration, and invasion of ovarian cancer cells, increased the expression of SQSTM1/p62 protein, decreased LC3II/LC3Ⅰ, inhibited the phosphorylation of Akt and mTOR proteins, and suppressed the expression of PI3K(p110ß) and Beclin1 proteins. The decrease in PXN expression also confirmed these changes. Thus, PXN is highly expressed during ovarian cancer and is associated with poor patient prognosis. It may promote ovarian cancer cell proliferation, migration, and invasion by inhibiting cellular autophagy via suppression of the p110ß/Vps34/Beclin1 pathway.

Infective endocarditis with anomalous origin of coronary arteries and an abnormal aortic root bulge: A case report.

Background: The aortic bulge sign possibly indicates an arterial aneurysm, pseudoaneurysm, aortic dissection, or aortic diverticulum. The aortic diverticulum is a congenital abnormality of the aorta, mainly known as an aneurysmal remnant of the dorsal fourth aortic arch or ductus arteriosus. However, the diverticulum of another part of the aorta has rarely been reported. Case summary: We report a case of a 24-year-old male with a history of oral ulcer presented with recurrent hyperpyrexia and chest pain. Echocardiography and computed tomography showed the anomalous origin of the coronary arteries, aortic valve vegetations, and a bulge at the aortic root. The patient then received a Bentall procedure. The aorta and aortic valves were replaced by a valved conduit. The bulge with a normal arterial wall at the aortic root was considered to be a diverticulum. The infective endocarditis was verified as a secondary oral-derived streptococcal infection. The patient was discharged 15 days after surgery. Post-operative echocardiography had no positive findings. Conclusion: Our case report highlights the role of multimodal cardiovascular imaging for the diagnostic workup of rare disorders, such as the presence of a diverticulum in the aortic root in a patient with endocarditis and anomalous origin of the right coronary artery.

Construction and comprehensive analysis of a curoptosis-related lncRNA signature for predicting prognosis and immune response in cervical cancer.

Cuproptosis (copper-ion-dependent cell death) is an unprogrammed cell death, and intracellular copper accumulation, causing copper homeostasis imbalance and then leading to increased intracellular toxicity, which can affect the rate of cancer cell growth and proliferation. This study aimed to create a newly cuproptosis-related lncRNA signature that can be used to predict survival and immunotherapy in patients with cervical cancer, but also to predict prognosis in patients treated with radiotherapy and may play a role in predicting radiosensitivity. First of all, we found lncRNAs associated with cuproptosis between cervical cancer tumor tissues and normal tissues. By LASSO-Cox analysis, overlapping lncRNAs were then used to construct lncRNA signatures associated with cuproptosis, which can be used to predict the prognosis of patients, especially the prognosis of radiotherapy patients, ROC curves and PCA analysis based on cuprotosis-related lncRNA signature and clinical signatures were developed and demonstrated to have good predictive potential. In addition, differences in immune cell subset infiltration and differences in immune checkpoint expression between high-risk and low-risk score groups were analyzed, and we investigated the relationship between this signature and tumor mutation burden. In summary, we constructed a lncRNA prediction signature associated with cuproptosis. This has important clinical implications, including improving the predictive value of cervical cancer patients and providing a biomarker for cervical cancer.

The novel delivery-exosome application for diagnosis and treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic degenerative disease characterized by persistent systemic synovitis, with a high risk of stiffness, pain, and swelling. It may affect the other extra-articular tissues. There is no ideal treatment for this disease at present, and it can only be controlled by medication to alleviate the prognosis. Exosomes are small vesicles secreted by various cells in the organism under normal or pathological conditions, and play a role in immune response, antigen presentation, cell migration, cell differentiation, tumor invasion and so on. Due to the adverse effects of conventional drugs and treatments in the treatment of RA, exosomes, as a nanocarrier with many advantages, can have a great impact on the loading of drugs for the treatment of RA. This article reviews the role of exosomes in the pathogenesis of RA and the progress of exosome-based therapy for RA.

Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer.

In ovarian carcinogenesis and progression, long non-coding RNAs (lncRNAs) have been shown to have a role, although the underlying processes remain a mystery. By modulating the degree of autophagy in ovarian cancer cells, we sought to learn more about the function lncRNA HOXA11-AS plays in the development of ovarian cancer. The expression of HOXA11-AS in ovarian normal cells and ovarian cancer cell lines was measured using R package and qRT-PCR. Ovarian cancer cells expressed HOXA11-AS substantially higher than normal cells, while cisplatin-resistant cells expressed HOXA11-AS significantly higher than ovarian cancer cells. Next, we studied the prognostic data of HOXA11-AS in ovarian cancer in the Tissue Cancer Genome Atlas (TCGA). In the next step, lentiviral transfection of ovarian cancer cells A2780, OVCAR3, and A2780/DDP (cisplatin-resistant) were performed, and HOXA11-AS knockdown was found to significantly inhibit cell viability, migration, and invasion of A2780 and OVCAR3 cells, and promote apoptosis by CCK-8 assay, transwell assay, cell cycle, and apoptosis assay, and promoted the sensitivity of A2780/DDP cells to cisplatin. It has been shown by the western blot test that HOXA11-AS knockdown increases the amount of cellular autophagy in cells. In contrast, adding the autophagy inhibitor 3-methyladenine (3-MA) to HOXA11-AS cells knocked down in vivo reduced its anti-tumor properties. As a whole, this study found that HOXA11-AS knockdown increased the expression of autophagy-related proteins and improved cisplatin sensitivity, decreased ovarian cancer cell proliferation, and promoted cell apoptosis. This study provides new insights into the role of HOXA11-AS in ovarian cancer regulation.

Effects of heat-sensitive moxibustion combined with naprapathy and warming needle moxibustion combined with naprapathy in patients with periarthritis of shoulder.

OBJECTIVE: To evaluate the effects of heat-sensitive moxibustion (HSM) combined with naprapathy and warming needle moxibustion (WNM) combined with naprapathy on shoulder function and serum levels of calcitonin gene-related peptide (CGRP), substance P (SP), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) in patients with periarthritis of shoulder (POS). METHODS: From July 2017 to July 2020, sixty patients with POS admitted to our hospital were selected as the study subjects, and divided into HSM group (n=29) receiving HSM combined with naprapathy and WNM group receiving WNM combined with naprapathy (n=31). The changes in shoulder function, degrees of pain and serum levels of CGRP, SP, TNF-α and IL-2 were compared between the two groups. RESULTS: After treatment, the scores of myodynamia, pain, range of motion (ROM) of shoulder joint and activities of daily living (ADLs) were improved in both groups (P<0.05), and the scores in HSM group were remarkably higher than those in WNM group (P<0.05). Visual analogue scale (VAS) scores after 3 courses of treatment were lower than those after 1 and 2 courses of treatment respectively (P<0.05), and the VAS scores in HSM group were markedly lower than those in WNM group after 1, 2, and 3 courses of treatment (P<0.05). After treatment, the serum levels of CGRP, SP, TNF-α and IL-2 were decreased in both groups (P<0.05), and the levels in HSM group were noticeably lower than those in WNM group (P<0.05). CONCLUSION: HSM combined with naprapathy is superior to WNM combined with naprapathy in inhibition of inflammatory factors of pain and serum inflammatory factors, alleviating the pain and promoting the restoration of shoulder function in patients with POS.

Reviewing Propolis with Multi-components in the Treatment of Oral Diseases through Multi-pathways and Multi-targets.

Propolis is a natural product made from the mixture of plant resin, saliva and wax collected by bees. It has been studied and concerned because of its high medicinal value and broad application prospects. Propolis has complex components, which can act on the body through multi-pathways and multi-targets to play the role of antibacterial, anti-inflammatory, anti-tumor and so on, and it can be used as an important resource for the prevention and treatment of oral diseases. In this review, we mainly reviewed components of propolis and its physiological activities against oral diseases, as well as the new dosage forms and applications of propolis in oral treatment. The purpose of this review is to explore the advantages of propolis in the treatment of oral diseases and the wide application of propolis in the field of oral health.

Echocardiographic and pathomorphological features in fetuses with ductal-dependent congenital heart diseases.

OBJECTIVE: To individually analyze echocardiographic features in fetuses with ductal-dependent congenital heart diseases (DDCHD) and to verify the anatomical characteristics corresponding to the echocardiogram scan views. BACKGROUND: Ductal-dependent congenital heart diseases depends on the ductus arteriosus (DA) remaining open to maintain suitable pulmonary or systemic circulation after birth. An accurate diagnosis using prenatal echocardiography has important clinical significance in evaluating disease prognosis and ensuring timely treatment. METHODS: Fetuses were followed in the prenatal and postpartum periods via echocardiography. The results of postpartum echocardiography or autopsy specimens were compared with the prenatal echocardiography findings. RESULTS: One hundred and eight fetuses displayed various types of DDCHD including 66 fetuses with ductal-dependent pulmonary circulation, and 42 fetuses with ductal-dependent systemic circulation. Prenatal echocardiography revealed the typical characteristics of no forward flow signal from right ventricular outflow tract to the pulmonary trunk proximally and a reverse flow in the DA in most fetuses for ductal-dependent pulmonary circulation, a reverse flow in the transverse aortic arch for aorta atresia, and a loss of continuity between aortic arch and descending aorta for interruption of the aortic arch (IAA). All 108 fetuses displayed various types of complex CHD, including right ventricular dysplasia with pulmonary atresia (PA), severe Ebstein anomaly, double outlet right ventricle with PA, tetralogy of fallot with PA, single ventricle with PA or aorta atresia, hypoplastic left heart syndrome, and IAA. CONCLUSIONS: The identification of reverse flow in the aortic arch or DA aids in the subsequent accurate diagnosis of DDCHD associated with complex malformation of the heart.

The Effect of Compound Sophora on Fluorouracil and Oxaliplatin Resistance in Colorectal Cancer Cells.

Fluorouracil (5-FU) and oxaliplatin (L-OHP) are the most commonly used chemotherapy drugs for colorectal cancer, though resistance is common. Compound Sophora injection is a traditional Chinese medicine that can protect the liver against oxidation, improve immunity, and enhance sensitivity to chemotherapy; it may have an effect of reversing resistance in 5-FU- and L-OHP-resistant gastric cancer cells (5-FU/SW480 and L-OHP/SW480, respectively). A concentration gradient experiment was performed to identify a nontoxic dose of compound Sophora injection. 5-FU/SW480 and L-OHP/SW480 cells were treated with the nontoxic dose of compound radix Sophorae injection for 48 h, and changes in drug resistance to 5-FU and L-OHP were detected. Alterations in apoptosis and the cell cycle were assessed, as were the mRNA and protein levels of permeability glycoprotein (P-gp), annexin A1 (ANXA1), and ATP-binding cassette superfamily G member 2 (ABCG2). Flow cytometry showed a reduction in the number of cells in the G1 phase and an increase of cells in the S phase (P < 0.05). mRNA and protein expression of P-gp and ABCG2 was significantly higher in 5-FU/SW480 and L-OHP/SW480 cell lines, and ANXA1 expression decreased significantly (P < 0.05). Compound Sophora injection can reverse the drug resistance of 5-FU/SW480 and L-OHP/SW480 cell lines to 5-FU and L-OHP, respectively, possibly through a mechanism involving reduced expression of P-gp and ABCG2 but enhanced expression of ANXA1, which is the basis for the identification of clinical drug resistance in colorectal cancer.

Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer.

BACKGROUND: Combined anthracycline-trastuzumab chemotherapy has been associated with LV dysfunction. We aimed to assess early changes in left ventricular (LV) and right ventricular (RV) mechanics associated with combined anthracycline-trastuzumab treatment for breast cancer. As well as explore whether early changes in 2-dimensional (2D)-speckle tracking echocardiography (STE) could predict later chemotherapy-induced cardiotoxicity. METHODS: Sixty-six patients with breast cancer who received anthracycline-trastuzumab treatment were included (mean [±SD] age, 52 [9] years). Echocardiograms were available for analysis with 2D-STE at the following time points: pretreatment (T0), first cycle (T1), and second cycle (T2) of combined chemotherapy. All patients had a normal pretreatment LV ejection fraction (LVEF). Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography. RESULTS: Cardiotoxicity developed in 13 of the 66 patients (20%). The mean (±SD) LVEF at T0 was 66% (±6); at T1 60% (±7); and at T2, 54% (±6). For the 53 patients without cardiotoxicity, the LVEF was 65% (±4%) at T0, 63% (±5%) at T1, and 62% (±4) at T2. Global longitudinal strain (GLS) at T1 was the strongest indicator of subsequent cardiotoxicity (area under the curve, 0.85; cutoff value, - 14.06; sensitivity, 91%; specificity, 83%; P = .003). Compared with baseline (T0), left ventricular longitudinal strain, LV circumferential strain, circumferential peak systolic strain rate (SR), circumferential peak early diastolic SR, right ventricular longitudinal strain, and longitudinal peak systolic SR at T1 and T2 were reduced significantly in patients with cardiotoxicity (P < .05). CONCLUSIONS: Anthracycline-trastuzumab treatment leads to early deterioration of LV GLS, circumferential strain, and systolic SR. Right ventricular GLS and SR were also affected. Early changes in GLS are good predictors of subsequent development of anthracycline-trastuzumab-induced cardiotoxicity.

Protective effects of Kangxian ruangan capsule against nonalcoholic fatty liver disease fibrosis in rats induced by MCD diet.

Kangxian ruangan (KXRG) capsule is a classical formula containing various herbals that play a vital role of replenishing spleen and warming Yang. Traditional Chinese medicine believes that insufficiency of the spleen, damp-heat, and phlegm and stasis are the key factors to nonalcoholic fatty liver disease (NAFLD). The objective of this study was to investigate the effects of KXRG capsule on NAFLD fibrosis rats induced by MCD diet. The liver functions (ALT, AST and GGT) and levels of blood lipids (CHOL and TG) in each treatment group rats were significantly decreased, especially those in H-KXRG group. At the same time, the KXRG capsule alleviated the inflammatory response, histopathological changes and liver fibrosis of NAFLD fibrosis rats. In addition, the apoptosis of liver cells induced by diet was obvious via TUNEL staining. However, KXRG capsule reversed that negative change. Moreover, the levels of pro-apoptotic proteins (Caspase 3, 8, 9 and Bax) were reduced by exposure to KXRG capsule, except that the anti-apoptotic proteins (Bcl-2 and Bcl-XL) were elevated. In conclusion, KXRG relieved the progression of NAFLD fibrosis via maintaining the balance of TNF-α/IL-10 further relieving the inflammatory reaction, and regulating the balance of Bcl-2/Bax or Bcl-XL/Bax in a positive direction further activating damaged hepatocytes.

Inhibition of prostate cancer growth by immunization with a GM-CSF-modified mouse prostate cancer RM-1 cell vaccine in a novel murine model.

Advanced prostate cancer is difficult to treat owing to a lack of effective approaches for disrupting immune tolerance. C57BL/6 male and female mice implanted with viable RM-1 cells represent a novel murine model of advanced prostate cancer for studying antitumor effects following immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-modified RM-1 cell vaccine, which has been described previously. In vitro cytotoxic activity and cytokine secretion experiments were conducted to investigate the antitumor response. The cytotoxicity profile of splenocytes from female mice immunized against RM-1 cells primarily involved cytotoxic T lymphocyte (CTL) lysis and, to a lesser extent, natural killer (NK) cell lysis. NK cell lysis was also observed in males, which exhibited no evidence of CTL lysis. The secretion of interferon-γ in the GM-CSF-modified cell vaccine group was significantly increased compared with the other groups. The level of interleukin-4 was low. To investigate the antitumor immune response further, cluster of differentiation 4 (CD4) T cells and CD8 T cells were analyzed in the spleens and tumors of female mice receiving the GM-CSF-modified RM-1 cell vaccine. Unlike female mice, males exhibited the highest proportion of NK cells in the spleen. NK cells were not detected in the tumor tissue in any of the groups. The difference between the sexes may explain the specificity of the immune response, as females are intolerant to prostate antigens whereas males are. This model is clinically relevant as it translates to human immunology and offers an effective and convenient method for studying immunotherapy for prostate cancer.

Use of transesophageal echocardiography and contrast echocardiography in the evaluation of cardiac masses.

OBJECTIVES: To determine whether the combination of transesophageal echocardiography (TEE) and contrast echocardiography (CE) accurately diagnose suspected cardiac masses using large sample data. METHODS: Patients with cardiac masses undergoing surgical treatment were enrolled in this study. Routine transthoracic echocardiography (TTE) and TEE examinations were carried out, and CE examinations were carried out when needed. All patients' clinical data and imaging features were retrospectively reviewed. Surgery and histopathology served as the gold standard for diagnosing cardiac masses. RESULTS: A total of 252 consecutive patients were included in this study. Sixteen patients were lost to follow-up and were excluded from the study. The combinations of TEE and CE yielded the correct pathologic diagnosis in 225 of 230 patients (97.8%), while CT yielded the correct pathologic diagnosis in 122 of 141 patients (86.5%), p<0.01. TEE yielded the correct pathologic diagnosis in 219 of 226 patients (96.9%), and CE yielded the correct pathologic diagnosis in 45 of 48 patients (93.8%). TTE alone yielded the correct pathologic diagnosis in 163 of 236 patients (69.1%), p<0.001 for all. TEE imaging provided detailed and precise information regarding cardiovascular morphology, anatomy, hemodynamics and function, and CE provided information regarding tissue characteristics without subjecting patients to radiation exposure. CONCLUSIONS: The combination of TEE and CE is feasible for the detection of suspected cardiac masses, especially in diagnosing and differentiating between benign and malignant lesions.

Speckle tracking echocardiography predicts early subclinical anthracycline cardiotoxicity in patients with breast cancer.

PURPOSE: This study aimed to assess the early changes of left ventricular (LV) and right ventricular (RV) mechanics associated with anthracycline treatment for breast cancer and to determine whether two-dimensional speckle tracking echocardiography (2D-STE) analysis could predict chemotherapy-induced cardiotoxicity. BACKGROUND: Anthracycline generates progressive LV dysfunction associated with a poor prognosis. Early detection of minor change of myocardial mechanics is thus important. METHODS: Pretreatment (T0), first (T1), and second (T2) on-treatment echocardiograms were available for analysis with 2D-STE. All patients had normal pretreatment left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a drop in LVEF to ≤53% or an absolute decrease of 10% on a follow-up echocardiogram. Analysis of variance receiver operating curve and area under the curve (AUC) analysis was performed. RESULTS: Eighty-six patients with breast cancer who received anthracycline treatment were included. Compared with T0, LV and RV global longitudinal strain (GLS), and LV global circumferential strain (GCS) at T1 and T2 were reduced significantly (p < 0.005 for all). There was a significant decrease in the LV GLS with increasing age at both T1 and T2 (p < 0.05 for all). GLS at T1 (AUC 0.83; cutoff -14.06; sensitivity 83%; specificity 84%; p = 0.0033) and at T2 (AUC 0.90; cutoff -13.84; sensitivity 93%; specificity 84%; p < 0.0001) was the strongest indicator of subsequent cardiotoxicity. CONCLUSIONS: Anthracycline treatment induces early deterioration of LV global longitudinal and circumferential strain, involving also the RV. Early change in the GLS seems to be a good predictor of the development of chemotherapy-induced cardiotoxicity. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:222-230, 2017.