Downregulation of p70S6K Enhances Cell Sensitivity to Rapamycin in Esophageal Squamous Cell Carcinoma

It has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent studies. In the present study, we explored the measures to improve the sensitivity of ESCC cells to rapamycin and identified the clinical significance of the expression of phosphorylated p70S6K (p-p70S6K). The results showed that, after downregulating the expression of p70S6K and p-p70S6K by p70S6K siRNA, the inhibitory effects of rapamycin on cell proliferation, cell cycle, and tumor growth were significantly enhanced in vitro and in vivo. Furthermore, p-p70S6K had strong positive expression in ESCC tissues and its expression was closely related to lymph node metastasis and the TNM staging. These results indicated that p-p70S6K may participate in the invasion and metastasis in the development of ESCC and downregulation of the expression of p-p70S6K could improve the sensitivity of cells to rapamycin in ESCC

Effects of Thioglycolic Acid on Parthenogenetic Activation of Xenopus Oocytes

BACKGROUND: Existing in Permanent-wave solutions (PWS), thioglycolic acid (TGA) is widely used in hairdressing industry for its contribution to hair styling. However, the toxicity of TGA, especially its reproductive toxicity, gradually calls the attention of more and more researchers. METHOD: In this work, xenopus oocytes were pretreated with different concentration of TGA, and then activated by calcium ionophore A23187. During culture, the oocytes activation rates were taken note at different time after adding calcium ionophore A23187. At the end of the culture period, the nuclear status was detected under confocal microscope. In addition, some other samples were collected for Western-Blotting analysis. RESULT: TGA significantly inhibited the oocytes activation rate and pronuclear formation. It may be resulted from the inhibition of the degradation of p-ERK1, Mos and CyclinB2. CONCLUSION: TGA inhibits in vitro parthenogenetic activation of xenopus oocytes with inhibited the degradation of proteins involved in mitogenic-activated protein kinase (MAPK) and maturation-promoting factor (MPF) pathways

Targeted Inhibition of mTOR Signaling Improves Sensitivity of Esophageal Squamous Cell Carcinoma Cells to Cisplatin

mTOR is an evolutionarily conserved serine-threonine kinase with a central role in cell growth, invasion, and metastasis of tumors, and is activated in many cancers. The aims of this study were to investigate the expression of mTOR in ESCC tissues and its relationship with progression of ESCC and measure the changes of sensitivity of ESCC cells to cisplatin after cells were treated with mTOR siRNA by WST-8 assays, TUNEL, RT-PCR, and western blots in vitro and in vivo. The results showed that the expression of mTOR was higher in ESCC specimens than that in normal esophageal tissues and its expression was closely correlated with the TNM stage of ESCC. mTOR siRNA significantly increased the sensitivity of the EC9706 cells to cisplatin at proliferation in vitro and in vivo. The growth of ESCC xenografts was significantly inhibited by mTOR siRNA or cisplatin, and the cell number of apoptosis was obviously increased after xenografts were treated with mTOR siRNA or cisplatin alone, especially when mTOR siRNA combined with cisplatin. The present study demonstrates that the expression of mTOR has important clinical significance and inhibition of mTOR pathway by mTOR siRNA can improve the sensitivity of ESCC cells to cisplatin

Heat shock protein 90: biological functions, diseases, and therapeutic targets

Abstract Heat shock protein 90 (Hsp90) is a predominant member among Heat shock proteins (HSPs), playing a central role in cellular protection and maintenance by aiding in the folding, stabilization, and modification of diverse protein substrates. It collaborates with various co‐chaperones to manage ATPase‐driven conformational changes in its dimer during client protein processing. Hsp90 is critical in cellular function, supporting the proper operation of numerous proteins, many of which are linked to diseases such as cancer, Alzheimer's, neurodegenerative conditions, and infectious diseases. Recognizing the significance of these client proteins across diverse diseases, there is a growing interest in targeting Hsp90 and its co‐chaperones for potential therapeutic strategies. This review described biological background of HSPs and the structural characteristics of HSP90. Additionally, it discusses the regulatory role of heat shock factor‐1 (HSF‐1) in modulating HSP90 and sheds light on the dynamic chaperone cycle of HSP90. Furthermore, the review discusses the specific contributions of HSP90 in various disease contexts, especially in cancer. It also summarizes HSP90 inhibitors for cancer treatment, offering a thoughtful analysis of their strengths and limitations. These advancements in research expand our understanding of HSP90 and open up new avenues for considering HSP90 as a promising target for therapeutic intervention in a range of diseases

Inhibition of autophagy improves resistance and enhances sensitivity of gastric cancer cells to cisplatin

Autophagy plays critical roles in tumorigenesis, while the effects of autophagy on chemoresistance of cancer cells had great disparity. This study aims to explore the impacts of autophagy on the sensitivity and resistance of gastric cancer cells to cisplatin (DDP). We firstly demonstrated that there was stronger autophagy activity in gastric cancer SGC-7901 cells than that in DDP-resisting SGC-7901/DDP cells. Then, we discovered that inhibiting autophagy by chloroquine (CQ) significantly enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP to SGC-7901 and SGC-7901/DDP cells. Moreover, CQ could partially reverse the resistance of SGC-7901/DDP cells to DDP in a concentration-dependent manner. However, the autophagy inducer everolimus (RAD001) had no obvious effects on the sensitivity of gastric cells to DDP. Mechanistically, we demonstrated that CQ might enhance the sensitivity of SGC-7901cells and improve the resistance of SGC-7901/DDP cells to DDP through inhibiting the mTORC1 pathway, especially to SGC-7901/DDP cells. Additionally, we found interfering Beclin-1 using Beclin-1 shRNA also enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP on gastric cancer cells by inhibiting phosphorylation of Akt. Our study shows that inhibiting autophagy could improve the chemoresistance and enhanced sensitivity of gastric cancer cells to DDP and provide a rationale for the administration of cisplatin combined with CQ for treating patients with gastric cancer.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Dynamic Distribution of Skin Microorganisms in Donkeys at Different Ages and Various Sites of the Body

Considerable evidence suggests that the skin microbiota is not only important and complex in humans and other mammals but also critical for maintaining health and skin homeostasis. To date, studies on the skin microorganisms of donkeys are surprisingly rare. To investigate the dynamic changes in commensal microbial communities on the skins of healthy donkeys throughout the growing period, skin and soil samples were collected from 30 healthy Dezhou donkeys (ranging from 1, 6, 12, 24 to 48 months of age) and their corresponding breeding sheds on the farm. All samples were analysed for high-throughput sequencing of the 16S rRNA and ITS to characterize the skin microbiota of healthy donkeys and compare the differences in skin microbiota among donkeys of different ages. There were notable differences in the proportions of various genera (including bacteria and fungi) between dorsal and abdominal skin with increasing age. The comparison of the skin microbial communities among these groups revealed that Staphylococcus was mainly enriched in the early growing stage (1 and 6 months), while the relative abundance of Streptococcus was higher in both the 1- and 48-month-old age groups. Moreover, some bacteria and commensal fungi, such as Staphylococcus and Trichosporon, were found to be positively correlated between the skin and the environment. This is the first study to investigate the dynamic changes in skin microbiota diversity and composition in donkeys of different ages and at different sites of the body. Furthermore, this study provides insights into the dynamic alterations in skin microbes during a donkey’s growth and characterizes the profiles of bacterial and fungal communities across a donkey’s body regions (dorsal and abdomen)

Developing a BOPPPS (Bridge-in, Objectives, Pre-assessment, Participatory Learning, Post-assessment and Summary) model combined with the OBE (Outcome Based Education) concept to improve the teaching outcomes of higher education

Abstract The teaching objectives of traditional approaches in higher education emphasize mostly students’ mastery of knowledge and have insufficient directionality to social needs. In this study, we developed a BOPPPS (Bridge-in, Objectives, Pre-assessment, Participatory Learning, Post-assessment and Summary) teaching model combined with the OBE (Outcome Based Education) concept to enhance the teaching outcomes. Firstly, based on the graduation requirements and professional training objectives of students, we divided the course objectives into three dimensions (knowledge, ability and quality), and further specified into index points. Then, the teaching content of each chapter was set to correspond with the index points. Finally, the BOPPPS teaching model was used to meet each requirement. Clinical biochemistry testing course was used as a model to assess the effects of the teaching reform. After the class, the teaching effect was analyzed based on the questionnaire surveys from the students and their scores of both the chapter and final examinations. The results showed that compared with the traditional approach, the BOPPPS teaching model combined with the OBE concept has demonstrated a notable enhancement in student engagement, and significant improvement of their mastery of knowledge, application skills, and problem-solving abilities. The examination scores of the BOPPPS group were markedly higher than those of the traditional group. Moreover, the difference between the two groups diverse assessment scores was much bigger than that between the two group examination scores. Our study indicates that the BOPPPS teaching model combined with the OBE concept is a highly effective teaching model for enhancing the learning effectiveness of students

The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells

<div><p>Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total protein (TP) and albumin (ALB) indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.</p></div