ABSTRACT
The quantum steering as an intermediate form of quantum correlations, has various peculiarities differing from the Bell nonlocality and the quantum entanglement. In a specific scenario, each side of the observer shares one of the two entangled qubits, steering can be witnessed simultaneously between any two observers from different sides by performing weak or projective measurements successively, with independently chosen and unbiased inputs. Here, we demonstrate this steering scenario experimentally to simultaneously witness quartic Einstein-Podolsky-Rosen steerings of two successive observers between each side with the entangled pair with a state fidelity of 97.6% compared with a maximally-entangled one.
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Artificial intelligence (AI) technology has made leaps and bounds since its invention. AI technology can be subdivided into many technologies such as machine learning and deep learning. The application scope and prospect of different technologies are also totally different. Currently, AI technologies play a pivotal role in the highly complex and wide-ranging medical field, such as medical image recognition, biotechnology, auxiliary diagnosis, drug research and development, and nutrition. Colorectal cancer (CRC) is a common gastrointestinal cancer that has a high mortality, posing a serious threat to human health. Many CRCs are caused by the malignant transformation of colorectal polyps. Therefore, early diagnosis and treatment are crucial to CRC prognosis. The methods of diagnosing CRC are divided into imaging diagnosis, endoscopy, and pathology diagnosis. Treatment methods are divided into endoscopic treatment, surgical treatment, and drug treatment. AI technology is in the weak era and does not have communication capabilities. Therefore, the current AI technology is mainly used for image recognition and auxiliary analysis without in-depth communication with patients. This article reviews the application of AI in the diagnosis, treatment, and prognosis of CRC and provides the prospects for the broader application of AI in CRC.
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Frostbites are cold tissue damages frequently observed at high altitudes and under extremely cold conditions. Though their incidence rate is low, the resulting impact in affected patients can be very serious, often leading to amputations. Clinical management and the prediction of outcome can be of utmost importance to frostbite patients. A possible use of stem cell-derived extracellular vesicles (EVs) has been suggested for cutaneous wound healing and we, therefore, tested their use for the treatment of deep frostbite wound. To this end, the impacts of hHPC-derived EVs were evaluated in an in vivo animal model comprising of Kunming female mice as well as studied in vitro for the mechanism. We first characterized the EVs and these hHPC-derived EVs, when applied to treat frostbite wounds, accelerated wound healing in the in vivo animal model, as assessed by wound closure, re-epithelization thickness, collagen density and the expression of Collagen I and α-SMA. The proliferation and migration of human skin fibroblasts was also found to be increased by EVs in the in vitro experiments. The H2O2-induced apoptosis cell model, established to simulate the post-frostbite injury, was inhibited by EVs, with concomitant increase in the expression of Bcl-2 and decreased expression of Bax, further confirming the findings. Our novel results indicate that the application of EVs might be a promising strategy for deep frostbite wound healing.
Subject(s)
Extracellular Vesicles , Frostbite , Animals , Apoptosis , Cell Proliferation , Collagen , Extracellular Vesicles/metabolism , Female , Fibroblasts/metabolism , Frostbite/therapy , Humans , Hydrogen Peroxide , Mice , Stem Cells/metabolism , Wound HealingABSTRACT
BACKGROUND: Gastrointestinal (GI) metastasis from breast cancer (BC) is rarely encountered in clinical practice. Nonspecific symptoms and long intervals make early diagnosis difficult. Therefore, increased awareness of GI metastasis secondary to BC and a deep understanding of the clinical and pathological features, and intervention for GI metastasis are fundamental to avoid delay in correct diagnosis and management. CASE SUMMARY: The present report discusses the case of a Chinese female patient aged 36 years. The patient presented with difficult defecation along with bloody stools and hypogastralgia. In 2015, she had undergone right modified radical mastectomy and axillary lymph node dissection in another hospital to treat the infiltrating ductal breast carcinoma pT1N1M0. The presenting symptoms were investigated by colonoscopy, which indicated a circumferential stricture in the lower rectum at 3 cm from the anal edge. Further investigation with positron emission tomography-computed tomography revealed an uptake of fluorodeoxyglucose within the distal rectum as well as in the left acetabulum. The samples from laparoscopic exploration were biopsied, which revealed metastases of BC. Immunohistochemical analysis of the tumor confirmed that the patient had rectal metastasis of infiltrating ductal BC. CONCLUSION: Rectal metastasis should be considered when patients with a history of BC present with changed bowel habits.
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Laparoscopic anterior resection of rectum (AR) is one of surgical approaches for deeply infiltrating endometriosis (DIE). Up to date, no clinical trials have clearly analyzed the short-term and long-term complications post-surgically, indications or feasibilities for surgical procedure, or post-operative recovery. The aims of this trial were to evaluate the indications for laparoscopic AR, the short-term and long-term complications post-surgically, post-operative recovery.We conducted a prospective study of 29 patients. They were divided into 2 groups. The period of follow-up was 12 months post-surgery. In our study, we recruited patents with laparoscopic AR experiencing failure of medical treatment (3 months) or associated infertility (>2cycles). The operative data and short term and long term complications were recorded. The outcomes of laparoscopic AR group were assessed by questionnaires, such as NRS (numeric rating scale), KESS (Knowles-Eccersley-Scott Symptom Questionnaire), VAS (visual analogue scale), WCS (Wexner constipation score) and ABS (Abdominal Bloating Score), which were compared with the outcomes of medicine group at set time points of baseline, 3 months, 6 months, 9 months and 12 months. The overall outcomes of the two groups were assessed with 5-point Likert Scale.Patients in surgery group were recovery rapidly without serious short term or long term complications. All of NRS, KESS, VAS, WCS, and ABS in surgery group were getting better greatly than that in medicine group (3.04â±â1.91 vs 5.41â±â3.01, 5.64â±â1.54 vs 7.01â±â1.03, 0.50â±â0.38 vs 3.58â±â2.01, 4.43â±â1.02 vs 8.92â±â2.45, and 0.61â±â0.34 vs 1.42â±â0.71) at 3 months post-operation. However, the advantage of surgery group was almost vanished at 12 months (4.02â±â2.53 vs 5.99â±â2.31, 7.42â±â3.17 vs 10.98â±â2.53, 1.59â±â1.3 vs 2.23â±â1.59, 6.01â±â2.53 vs 7.90â±â3.25, and 1.31â±â1.05 vs 1.39â±â1.02). Furthermore, we compared the overall outcomes between the 2 groups with 5-point Likert Scale, with confirmation of the advantage at 3 months post-surgically. Additionally, we compared these questionnaires, with the finding that VAS and 5-point Likert Scale of surgery group had the same changes. Finally, a table of indications for laparoscopic AR were tabulated according our clinical experience.Patients can receive benefit from both medicine and laparoscopic AR. However, laparoscopic AR has obvious advantage of rapid symptom relief. Further studies and clinical data collections are required for indications and feasibility of combined therapy.
Subject(s)
Endometriosis/drug therapy , Endometriosis/surgery , Laparoscopy , Rectal Diseases/drug therapy , Rectal Diseases/surgery , Adult , Endometriosis/pathology , Female , Humans , Postoperative Complications/epidemiology , Prospective Studies , Rectal Diseases/pathology , Time Factors , Young AdultABSTRACT
Perineal wound complications after APR have high morbidity in the colorectal surgical department. Although some approaches have been figured out to solve this clinical focus, the outcomes are still not satisfied. Herein, this prospective comparative clinical trial has been designed to evaluate a new surgical procedure of direct perineal wound full-thick closure (DPWC), compared with conventional perineal wound closure (CPWC), with hopes of making wound healing with less complications. In addition, an evaluation of an incision negative wound pressure therapy, as another focus in this field, was also analysed in the DPWC group. A total of 44 participants in our department were recruited from March 2018 to March 2020, divided into two groups randomly, CPWC group and DPWC group. The patients' characteristics, such as age, gender, BMI, smoking, alcohol consumption, comorbidities, CEA level, and high-risk of invasion, were recorded without statistical significance between the CPWC group and DPWC group. After the same standard abdominal phase, these two groups were performed in different perineal phases. And then, operative and postoperative outcomes were analysed with different statistical methods. Data on wound healing time and length of stay in the DPWC group were shorter than those in the CPWC group (P < .05). Furthermore, cases of wound infection within 30 days in the DPWC group were also less than that in the CPWC group (P < .05). However, no difference was found between the incisional negative pressure wound therapy assisted group (NPA group) and non- incisional negative pressure wound therapy assisted group (non-NPA group). During this study, hypoalbuminemia, as an independent high-risk factor, impacted perineal wound healing. (P = .0271) In conclusion, DPWC is a new surgical approach, which can lead to a better outcome than DPWC, and it can be another surgical procedure for clinicians. In addition, hypoalbuminemia should be interfered for avoiding perineal wound complications.
Subject(s)
Carcinoma , Proctectomy , Rectal Neoplasms , Humans , Perineum/surgery , Postoperative Complications , Prospective Studies , Rectal Neoplasms/surgery , Retrospective StudiesABSTRACT
RATIONALE: Among the various forms of colorectal carcinomas, primary signet ring cell carcinoma (SRCC) of rectum is infrequent. Primary SRCC with adenoma is even rarer. Due to its low morbidity and lack of obvious manifestations at early stages, it is difficult to make an early diagnosis and perform surgical intervention in time. Herein, we reported a case of primary SRCC with tubular adenoma of rectum and also performed a review of the literature of such cases, in hopes of expanding the general understanding regarding such cases. PATIENT CONCERNS: A 61-year-old male patient presented with rectal bleeding for 1 week. DIAGNOSES: A neoplasm could be palpated through a rectal examination, with a size of 4.0âcm by 3.0âcm, at a distance of 5âcm from the anal edge. Magnetic resonance imaging examination and colonoscopies were performed to confirm the finding, and 4 tissue specimens were obtained for histopathologic biopsy. The result of biopsy was high-grade intraepithelial neoplasia with an adenoma component. INTERVENTIONS: Surgical resection was performed, and histopathologic and immunohistochemical staining examination of the resection confirmed the diagnosis of SRCC with tubular adenoma. OUTCOMES: The patient was discharged from hospital 12 days postsurgery, without any complications. Further chemotherapy and supportive treatments were suggested to him and will be followed at a local hospital. LESSONS: Primary rectal SRCC has a rather low morbidity. Furthermore, a rectal SRCC with adenoma which was presenting in this case is even more rare. Besides lack of clinical characters, delay of diagnosis and treatment frequently occur. So far, a surgical procedure has still been one of the most effective treatments. Considering of metastasis and the poor prognosis, early diagnosis, in-time radical resection, and a comprehensive followed treatment are recommended for a higher 5-year overall survival.
Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Signet Ring Cell/diagnosis , Rectal Neoplasms/diagnosis , Adenocarcinoma/pathology , Carcinoma, Signet Ring Cell/pathology , Humans , Male , Mass Screening/methods , Middle Aged , Rectal Neoplasms/pathology , Rectum/pathology , Treatment OutcomeABSTRACT
The violation of the Bell inequalities implies that quantum mechanics cannot be interpreted using any local hidden variable theory. However, particular quantum states that can originally be described using a local hidden variable model surprisingly exhibit nonlocality by employing local filters before a standard Bell test is performed. This is referred to as hidden nonlocality. In this study, we provide the experimental demonstration of hidden nonlocality through linear optics towards the local states which are put forword by Hirsch et al., PRL 111, 160402 (2013). A class of local states is generated through a spontaneous parametric down-conversion process, and the violation of the Clauser-Horne-Shimony-Holt (CHSH)-Bell inequality is observed by applying local filters. Our experimental results confirm the superiority of local filters, and throw light on deep understanding the intriguing phenomena of hidden nonlocality and local states.
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OBJECTIVE: This work was aimed to investigate the effect of microRNA-141 (miR-141) overexpression in the jawbones of ovariectomized-induced osteoporosis rats and investigate the role of miR-141 in the Wnt/ß-catenin pathway. METHODS: Twenty-four female rats were randomly divided into the sham group, ovariectomized osteoporosis group (OP), miR-141 agonist group (miR-141), and miR-141 scramble group (Scramble). Bone mineral density (BMD) and pathological changes of the jaw were detected. Serum receptor activator of nuclear factor-B ligand (RANKL), osteoprotegerin, tartrate-resistant acid phosphatase (TRAP), and bone gla protein (BGP) levels were tested by ELISA. The expression of Runt-related transcription factor 2 (Runx2), and Osterix measured by immunohistochemistry and the expression of Wnt, ß-catenin, and Dickkopf1 (DKK1) proteins was measured by Western blot. Furhter, the Wnt agonist DKK2-C2, Wnt inhibitor Endostar were used to verify the effect of miR-141 overexpression on the Wnt/ß-catenin pathway. RESULT: Compared with the OP group, the content of osteoprotegerin increased while the levels of RANKL, BGP, TRAP decreased in the miR-141 and DKK2-C2 groups (p < 0.05). The levels of Runx2 and Osterix increased significantly in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). Interestingly, the protein expression of Wnt and ß-catenin increased while DKK1 was remarkably down-regulated in the miR-141 and DKK2-C2 groups when compared to the OP group (p < 0.05). In contrast to the miR-141 group, the above results were reversed after treatment with the Endostar (p < 0.05). CONCLUSION: Overexpression of miR-141 could inhibit the osteoporosis of jawbones in ovariectomized rats by activating the Wnt/ß-catenin pathway.
Subject(s)
Jaw/pathology , MicroRNAs/genetics , Osteoporosis/genetics , Wnt Signaling Pathway , Animals , Female , Intercellular Signaling Peptides and Proteins/metabolism , Osteoporosis/pathology , Ovariectomy , Rats , Rats, Sprague-Dawley , beta Catenin/metabolismABSTRACT
Cholangiocarcinoma (CCA) is a fatal malignant tumor of biliary epithelial cells involving intra- or extra-hepatic bile ducts. The prognosis of CCA is generally poor due to its diagnosis at the late stages. The currently employed chemotherapeutic agents do not increase the survival rate in patients with unresectable CCA. Accordingly, there is a need to identify new therapeutic agents for the effective management of intra- and extra-hepatic CCA. Clinical as well as preclinical studies have suggested the key role of the activation of Wnt/ß-catenin signaling pathway in the induction and progression of CCA. There is an up-regulation of different Wnt ligands including Wnt2, Wnt3, Wnt5, Wnt7 and Wnt10 along with redistribution of ß-catenin (more expression in the nucleus and lesser on the cell surface due to nuclear translocation of ß-catenin) in different types of malignant biliary tumors. Apart from the role of this pathway in the induction and progression of CCA, this pathway is also involved in inducing multidrug resistance by inducing the expression of P-glycoprotein efflux pump on the cancer cells. These deleterious effects of Wnt/ß-catenin signaling are mediated in association with other signaling pathways involving microRNAs (miRNAs), PI3K/AKT/PTEN/GSK-3ß, retinoic acid receptors (RARs), dickkopf-1 (DKK1), protein kinase A regulatory subunit 1 α (PRKAR1A/PKAI), (SLAP), liver kinase B1 (LKB1) and CXCR4. The selective inhibitors of Wnt/ß-catenin signaling may be potentially employed to overcome multidrug-resistant, fatal CCA. The present review discusses the role of Wnt/ß-catenin along with its relation with other signaling pathways in the induction and progression of CCA.
Subject(s)
Cholangiocarcinoma/metabolism , Wnt Signaling Pathway/drug effects , Wnt Signaling Pathway/physiology , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Ducts/pathology , Bile Ducts, Intrahepatic/metabolism , Bile Ducts, Intrahepatic/pathology , Cell Line, Tumor , Cell Proliferation , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/physiopathology , Glycogen Synthase Kinase 3 beta/metabolism , Humans , MicroRNAs , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Wnt Signaling Pathway/genetics , beta Catenin/metabolismABSTRACT
The objective of this paper is to demonstrate, considering the experiences from Chinese people, if slow transit constipation (STC) can be accurately diagnosed, choosing patients qualifying for surgery, subtotal colectomy with antiperistaltic cecosigmoidal anastomosis (STC-Anti-CSA) may come with more acceptable short and long-term outcomes.A retrospective study was performed at a department of colorectal and anal surgery. A cohort of 29 patients were coming with up to 5 years' follow-up care, who were in a diverse range of age, BMI, laxative medicine histories, including both males and females. Pre-surgery work-up strictly followed a protocol designed to rule out the patients who were not suitable for surgery treatments. Classification of STC was followed after diagnosis. STC-Anti-CSA was performed in all cases. The operative time, blood loss, average post-operative length of stay (LOS), frequency of BMs, stool consistency and patients satisfaction, by using Wexner constipation score (WCS), numerical rating scale (NRS), and abdominal bloating score (ABS), over the study period were recorded.In this study, there were 14 males and 15 females, with mean age 51, and BMI from 20.14 to 31.62âkg/m. The period of laxative medicine history was 4.8 years (2-13 years). The mean operative time was 152â±â34âmin, and the mean perioperative blood loss was 123â±â51âmL. Average post-operative LOS (LOS) was 8 days. There were no severe post-operative complications, peri-operative mortality, anastomotic leaks, or revisions of the original surgery. Initial post-operative BMs averaged 6 times/day. During the period of 1 month to 12 months follow-up care, BMs fell down to 2 or 3 times/day. By the 1st to 3rd year follow-up care, BMs averaged 5 to 7 times/week. However, from the 4th year to 5th year, constipations recurred somehow. However, most patients were satisfied with their bowel patterns.STC-Anti-CSA can receive acceptable postoperative outcomes as long as the patients can be accurately diagnosed and classified as severe STC. Among the surgical procedures for STC, this procedure may be another suitable option, especially for Chinese people.
Subject(s)
Cecum/surgery , Constipation/surgery , Rectum/surgery , Adult , Aged , Anastomosis, Surgical , China , Colectomy , Female , Gastrointestinal Transit , Humans , Length of Stay , Male , Middle Aged , Operative Time , Quality of Life , Retrospective Studies , Treatment OutcomeABSTRACT
Sacrococcygeal pilonidal sinus is one of common diseases in general department. However, it is characterised, for surgeons, by high post-surgical recurrence and high incidence of post-surgical wound complications. Due to that fact, this retrospective randomised clinical study was designed to evaluate the surgical procedure effect of Z-plasty (ZP), compared with convention simple excision (SE). A total of 67 patients from May 2015 to May 2019 in our department were studied into two groups randomly, the group of ZP and the group of SE. The patients' characteristics, surgical data, hospital length of stay (LOS), and post-surgery complications were recorded. Statistical approaches were proceed with P-value analysis. The results are as follows. No significant differences were found between these two groups of the ages, gender distribution, Body Mass Index (BMI), smoking history, diabetes mellitus, and blood hypertension. The estimated blood loss, specimen volume, distance to anus, and drain output on the first day of post-surgery between the two groups were not statistically significant, either. However, surgical time in the ZP group was longer than that in the SE group (P < .0001). LOS in the ZP group was obviously shorter than that in the SE group (P = .0051). Furthermore, the patients of the ZP group were tending to suffer from fewer post-surgical complications than the ones of the SE group. In a conclusion, we hold the point view that the surgical procedure of ZP can lead a better outcome than SE because it demonstrated shortened LOS and fewer post-surgical complications.
Subject(s)
Pilonidal Sinus/surgery , Postoperative Complications/epidemiology , Suture Techniques/adverse effects , Adolescent , Adult , Algorithms , China , Female , Humans , Length of Stay , Male , Retrospective Studies , Sacrococcygeal Region , Treatment Outcome , Wound Healing , Young AdultABSTRACT
Einstein-Podolsky-Rosen steering is an intermediate relationship between entanglement and Bell nonlocality in the hierarchical structure of quantum nonlocality. To certify the steerability of the entangled state, Mermin steering inequality is supposed to be violated by exceeding the inequality bound of 2. We present an experimental generation of post-selected three-photon entangled states and witness a maximal violation of the inequality up to 3.50±0.05. In the context of observing the maximal violation of Mermin steering inequality which requires measuring on the GHZ state, we derive a tight lower bound on the GHZ-fidelity that can be certified from the Mermin steering inequality violation. From this bound, it follows that the violation of Mermin steering inequality by 3.5 certifies the GHZ-fidelity of 78.66% at least. On the other hand, the above maximal violation of Mermin steering inequality observed in our experimental setup is produced by a post-selected entangled state having the GHZ-fidelity of 87.25 ± 0.34% through quantum tomography.
ABSTRACT
BACKGROUND: The link between Apelin (APL)/APL receptor (APJ) and Jagged (JAG)/Notch signaling pathways in colorectal cancer (CRC) has been poorly investigated. APL/APJ system, a potent angiogenic factor, is up-regulated in a variety of cancers. It contributes to tumor angiogenesis, and correlates with progression of malignancy. JAG/Notch signaling also contributes to progression, proliferation and metastasis of multiple cancers, including CRC. Here we tested the hypothesis that APL/APJ system promotes CRC proliferation by up-regulating Notch3, thus allowing further binding of JAG1 to Notch3. MATERIALS AND METHODS: We used a variety of methods including Western blot, RT-qPCR, gene silencing, ELISA, immunofluorescence staining, to investigate the interaction between APL/APJ system and Notch3 signaling pathway in both surgically-resected specimens and CRC cell line LS180. RESULTS: We show that the expression of APL13, APJ, and Notch3 is elevated in CRC. We further demonstrate that APL13 can be secreted into culture media of LS180 cells, suggesting the existence of autocrine loop in CRC. Moreover, we found that APL13 stimulated expression of Notch3. Finally, we found that inhibition of either APJ or Notch3 prevents proliferation of LS180 cells. CONCLUSIONS: Our results suggest that APL13/APJ and JAG1/Notch3 signaling pathways are linked in CRC. These findings provide a new direction to the efforts targeting effective therapeutic and management approaches in the treatment of CRC.
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Oral tongue squamous cell carcinoma (OTSCC) is the most common oral malignancy with different histopathological symptoms and etiology of tumorigenesis. Migration and invasion is the most important characteristics of OTSCC, and limits tumor therapy in clinics. The epithelialtomesenchymal transition (EMT) signaling pathway is an important process in the progress of tumor cell migration and invasion. Previous studies have indicated that CXC chemokine receptor7 (CXCR7) promotes the progression and metastasis of tumor cells, presenting a potential target molecule for cancer therapy. The present study investigated the inhibitory effects of CXC chemokine7 (CXC7) on human OTSCC cells both in vitro and in vivo. The results demonstrated that the Tca8113 human OTSCC cell line expressed higher levels of CXC7 mRNA compared with the hNOE human normal oral epithelial cell line. MTT assays indicated that CXC7 suppressed Tca8113 cell growth, and the cytotoxicity of CXC7 was indicated as the cell survival of the negative control group was significantly decreased compared with the blank control and hNOE cells. Migration and invasion assays revealed that CXC7 inhibited Tca8113 cell local expansion and distant metastasis. In addition, the results demonstrated that the extracellular signalregulated kinase (ERK)/protein kinase B (AKT) signaling pathway was inhibited after CXC7 treatment in Tca8113 cells. Ncadherin, ECadherin, Snail and Slug expression levels in the ERK/AKT signaling pathway were inhibited in Tca8113 cells after treatment with CXC7. It was demonstrated that important extracellular matrix proteins involved in cell migration, including Slug, collagen type I and Vimentin, were significantly downregulated by CXC7 treatment. In conclusion, CXC7 inhibited growth and migration in OTSCC cells, mediated by the EMT signaling pathway. This suggests that CXC7 serves an inhibitory role in OTSCC migration, implicating CXCR7 as a promising biomarker for chemokine receptorbased drug development.
Subject(s)
Chemokines, CXC/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Signal Transduction/drug effects , Animals , Cadherins/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Chemokines, CXC/therapeutic use , Down-Regulation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Proto-Oncogene Proteins c-akt/metabolism , Receptors, CXCR/genetics , Receptors, CXCR/metabolism , Tongue Neoplasms/drug therapy , Tongue Neoplasms/metabolism , Tongue Neoplasms/pathology , Transplantation, HeterologousABSTRACT
Emerging evidence has demonstrated the altered expression of mRNAs in cancer development and progression. In this study, the precise role of miRNA-22 (miR-22) in colon cancer cells was investigated. Upon transfection with a miR-22 expression vector, the viability of HCT-116 human colon cancer cells was significantly reduced and tumor cell migration and invasion capacity were also suppressed. Computational in silico analysis predicted that T-cell lymphoma invasion and metastasis 1 (TIAM1) is a target gene of miR-22. This was confirmed by qRT-PCR and western blotting, which showed that miR-22 expression inhibited TIAM1 mRNA and protein expression, respectively. In addition, the expression of pro-invasive gene matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and pro-angiogenic protein vascular endothelial growth factor (VEGF) were also reduced by miR-22 expression. Collectively, these data suggest that miR-22 may act as a tumor suppressor in colon cancer, most likely by targeting TIAM1 expression.
Subject(s)
Cell Movement/genetics , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Guanine Nucleotide Exchange Factors/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , MicroRNAs/genetics , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms/enzymology , Genes, Tumor Suppressor , Guanine Nucleotide Exchange Factors/biosynthesis , Guanine Nucleotide Exchange Factors/metabolism , HCT116 Cells , Humans , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , MicroRNAs/metabolism , Neoplasm Invasiveness , RNA, Messenger/genetics , T-Lymphoma Invasion and Metastasis-inducing Protein 1 , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Microbial fermentation is a promising technology for hydrogen (H(2)) production. H(2) producers in marine geothermal environments are thermophilic and halotolerant. However, no one has surveyed an environment specifically for thermophilic bacteria that produce H(2) through Fe-Fe hydrogenases (H(2)ase). Using heterotrophic medium, several microflora from a seaweed bed associated with marine hot springs were enriched and analyzed for H(2) production. A H(2)-producing microflora was obtained from Sargassum sp., 16S rRNA genes and Fe-Fe H(2)ase diversities of this enrichment were also analyzed. Based on 16S rRNA genes analysis, 10 phylotypes were found in the H(2)-producing microflora showing 90.0-99.5 % identities to known species, and belonged to Clostridia, Gammaproteobacteria, and Bacillales. Clostridia were the most abundant group, and three Clostridia phylotypes were most related to known H(2) producers such as Anaerovorax odorimutans (94.0 % identity), Clostridium papyrosolvens (98.4 % identity), and Clostridium tepidiprofundi (93.1 % identity). For Fe-Fe H(2)ases, seven phylotypes were obtained, showing 63-97 % identities to known Fe-Fe H(2)ases, and fell into four distinct clusters. Phylotypes HW55-3 and HM55-1 belonged to thermophilic and salt-tolerant H(2)-producing Clostridia, Halothermothrix orenii-like Fe-Fe H(2)ases (80 % identity), and cellulolytic H(2)-producing Clostridia, C. papyrosolvens-like Fe-Fe H(2)ases (97 % identity), respectively. The results of both 16S rRNA genes and Fe-Fe H(2)ases surveys suggested that the thermophilic and halotolerant H(2)-producing microflora in seaweed bed of hot spring area represented previously unknown H(2) producers, and have potential application for H(2) production.
Subject(s)
Hot Springs/microbiology , Hydrogen/metabolism , Hydrogenase/metabolism , Iron-Sulfur Proteins/metabolism , Seaweed/metabolism , Seaweed/microbiology , Bacillales/classification , Bacillales/genetics , Clostridium/classification , Clostridium/genetics , Gammaproteobacteria/classification , Gammaproteobacteria/genetics , Hydrogenase/genetics , Indonesia , Iron-Sulfur Proteins/genetics , Metagenome , Molecular Sequence Data , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
Protein glycation inhibitors from Polygonatum odoratum rhizomes were investigated using a bioassay-guided procedure to characterize active compounds for preventing and treating diabetic complications. The EtOH extract and soluble fractions were evaluated using an in vivo model of renal advanced glycation end-product (AGE) accumulation in streptozotocin-induced diabetic rats and an in vitro bovine serum albumin-glucose assay. Three homoisoflavanones 3-(4'-hydroxybenzyl)-5,7-dihydroxy-6-methyl-8-methoxychroman-4-one (1), 3-(4'-hydroxybenzyl)-5,7-dihydroxy-6,8-dimethylchroman-4-one (2), and 3-(4'-methoxybenzyl)-5,7-dihydroxy-6-methyl-8-methoxychroman-4-one (3), isolated from the active CHCl3-soluble fraction of the EtOH extract, were subjected to in vitro bioassays to evaluate their inhibitory activities against AGE formation. All the isolates inhibited AGE formation more effectively than the positive control, aminoguanidine. These results indicate that pending further study these compounds could be used as novel natural product drug for mitigating diabetic complications.
Subject(s)
Glycation End Products, Advanced/antagonists & inhibitors , Isoflavones/pharmacology , Plant Extracts/pharmacology , Polygonatum , Rhizome , Animals , Biological Assay/methods , Diabetes Mellitus, Experimental/metabolism , Glycation End Products, Advanced/biosynthesis , Isoflavones/isolation & purification , Kidney/metabolism , Molecular Structure , Rats , Rats, WistarABSTRACT
OBJECTIVE: To investigate the biological behavioral effects of specific siRNA expression plasmids targeted against c-Myc and vascular endothelial growth factor (VEGF) on human colorectal cancer cell line Volo. METHODS: The expression plasmids with small interfering RNA (siRNA) aiming at c-Myc and VEGF were designed and constructed respectively, then transfected into Volo cells by eukaryocyte transfection technique. The protein expressions of c-Myc and VEGF were detected by Western blotting. Cellular proliferation, apoptosis, cycle distribution and invasion character were analyzed by tetrazolium bromide colorimetry (MTT), flow cytometry (FCM), TUNEL assay and matrigel invasion assay respectively. RESULTS: Enzymatic digestion and DNA sequencing confirmed that the c-Myc and VEGF specific siRNA expression plasmids were constructed successfully. After plasmids were transfected into cells, the protein expressions of c-Myc and VEGF were significantly down-regulated respectively as compared with control group (P<0.01). The cellular proliferation inhibitory rates in c-Myc siRNA group, VEGF siRNA group and c-Myc+VEGF group were (59.20+/-5.05)%, (32.31+/-3.48)% and (75.81+/-7.89)% respectively, which were higher than that in control group [(6.80+/-1.45)%] (all P<0.05). The cell apoptosis rate in above 3 groups were (40.50+/-4.37)%, (21.30+/-2.98)% and (62.59+/-9.66)% respectively, which were higher than that in control group [(2.90+/-0.36)%] (all P<0.05). The cell invasion rates in VEGF siRNA group and c-Myc+VEGF siRNA group were (7.34+/-3.65)% and (2.80+/-1.02)%, which were lower than that in control group [(18.57+/-7.46)%] (P<0.05). The effect of c-Myc+VEGF siRNA group was greater. CONCLUSIONS: The specific siRNA efficiently silences the expression of c-Myc and VEGF, subsequently, suppresses the cell proliferation, triggers the cell apoptosis and inhibits the cell invasiveness in these transfected colorectal cancer Volo cells. In addition, the synergism of siRNA-c-Myc and siRNA-VEGF in transfected cells can be found.