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Objective: Colon cancer with retroperitoneal abscess is a rare and easily misdiagnosed disease and has only been reported via case. There is an urgent need to conduct a dataset analysis for such patients, which is crucial to improving the survival rate and quality of life of these patients. Methods: Patients with colon cancer associated with retroperitoneal abscess were extracted from our hospital and the PubMed, EMBASE and Web of Science databases. Clinical information, including the patients' basic characteristics, clinical symptoms, laboratory tests, imaging examinations, treatment methods and prognosis was analyzed. Results: Sixty-one patients were analyzed, with an average age of 65 years. The proportions of right and left colon cancers were 63.9% and 36.1%, respectively. A total of 98.0% of the patients had adenocarcinoma. Many patients have insidious symptoms such as fever and weight loss. At the first medical visit, pain was the most common symptom (71%), with pain in the thigh (21.8%), abdomen (21.8%), and waist and back (14.5%) ranking among the top three. The misdiagnosis rate of the patients referred to our department was 75%, while the overall misdiagnosis rate in the literature was 43.9%. Laboratory tests show that these patients often have elevated white blood cells and anemia. CT examination showed that 87.2% of patients had an iliopsoas muscle abscess, and tumors were not simultaneously detected in 37.2%. A total of 33.9% of patients had local abscesses of the iliopsoas muscle, 26.4% had drainage into the subcutaneous tissue of the waist and upper buttocks, and 22.6% had drainage around the adductor muscle group of the thigh. These patients have a variety of treatments, and many patients have undergone multiple and unnecessary treatments. Thirteen patients died after surgery, and 6 died in the hospital, of whom four were patients undergoing direct surgery, and the other 7 died after discharge due to cachexia. Conclusion: Colorectal cancer with retroperitoneal abscess is a relatively rare and easily misdiagnosed subtype of colon cancer. It is more likely to occur in right-sided colon adenocarcinoma. The main clinical symptom is pain caused by the drainage of pus to the corresponding areas of the waist, abdomen, and legs. CT is the preferred diagnostic method. Actively treating the abscess and then transitioning to standard colon cancer treatment can prevent patient death and improve treatment quality.
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Background: Although transverse colon ptosis (TCP) is commonly diagnosed in patients with constipation, it has not attracted significant attention in the evaluation of constipation. Herein, we assessed the correlation between TCP-related radiological parameters and the severity of slow transit constipation (STC). Methods: This study was a single-center retrospective cohort study, with participants enrolled between 2012 and 2020 in Zhongnan Hospital of Wuhan University, China. STC was diagnosed according to Rome IV criteria and results of colonic transit test (CTT); healthy volunteers were also recruited as controls. All participants were examined using abdominal X-rays (AXRs) to acquire the radiological parameters related to TCP. Among these parameters, the degree of TCP (DTCP) was defined as the vertical distance from the top of the splenic flexure to the lowest point of the reverse colon. The Wexner Constipation Score and Hospital Anxiety and Depression Scale were used to assess clinical severity. After multivariable linear regression, the correlations between radiological parameters and severity of STC were investigated. We also explored the differences in radiological parameters between the operation and the conservative group. Results: The study included 139 patients with STC and 125 healthy people in as the normal control (NC). Patients with STC probably had larger DTCPs than those in the NC group (242.27±25.86 vs. 93.00±32.57 mm; P<0.001). Pearson correlation analysis showed that TCP-related parameters were consistent with the symptom severity of STC [e.g., parameter DTCP was strongly correlated with Wexner Constipation Score, with a ß coefficient (95% CI) of 8.63 (8.24-9.02), P<0.001]. Multivariable linear regression models showed that patients with a larger DTCP were more likely to undergo surgery (23.67; 95% CI: 1.40-45.94; P=0.04). Conclusions: TCP-related parameters, especially the DTCP, may serve as novel and feasible alternative indices for the assessment of STC. However, the potential value of DTCP in assisting the evaluation of STC needs to be confirmed in study with a larger sample size.
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Researchers have documented the negative effects of refractory chemicals and emergent pollutants in landfill leachate (LL) that cannot be degraded using conventional methods. The propagation, invasion, and deleterious effects of several LL hazards affect aquatic species, the environment, and food outlets, causing significant safety issues. These include cancer risks, chronic exposure, and reproductive consequences. Alternatively, solar energy is a sustainable solution for treating landfill leachate to benefit humans and the environment. In this work, a thorough bibliometric and systematic analysis of studies that employed solar energy for landfill leachate remediation over the past decade was conducted in order to determine trends, and future research areas. In addition to the energy demand, the economic aspect and the advantages of using solar power to treat landfill leachate were discussed. Additionally, the study gives specific suggestions for future research purposes and important problems. The reviewed literature revealed that combining solar-based physical-chemical and biological processes has proven to be the most efficient method for landfill leachate degradation. It also appears from the bibliometric study that more collaboration and contribution are needed to develop solar-based landfill leachate treatment. This study concludes that solar-powered landfill leachate remediation techniques would considerably increase the effectiveness of treated leachate reutilization, advancing the cause of environmental sustainability.
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Poluentes Químicos da Água , Humanos , Poluentes Químicos da Água/análise , Saneamento , Eliminação de Resíduos Líquidos/métodosRESUMO
BACKGROUND: Colonic stenting reduces morbidity and stoma formation for left-sided colon cancer obstruction, and a prolonged interval between stenting and surgery with neoadjuvant chemotherapy administered might result in a lower stoma rate and tumor reduction. OBJECTIVE: The study aimed to evaluate the short-term outcomes of elective surgery following colonic stenting compared with elective surgery following colonic stenting and neoadjuvant chemotherapy in patients with left-sided colon cancer obstruction. DESIGN: This is a prospective multicenter cohort study. SETTINGS: This study was conducted at 5 medical centers. PATIENTS: Patients ( n = 100) with acute left-sided colon cancer obstruction undergoing colonic stenting between December 2015 and December 2019 were included. INTERVENTIONS: Patients were assigned to the stenting-alone or chemotherapy group. MAIN OUTCOME MEASURES: The primary outcomes measured were laparoscopic surgery and stoma rate. RESULTS: Of the 100 patients who underwent colonic stenting, 52 were assigned to the stenting group and 48 were assigned to the chemotherapy group. No statistically significant differences were detected in stent-related complications. The adverse events associated with neoadjuvant chemotherapy were well tolerated. The level of hemoglobin (117.2 vs 107.6 g/L; p = 0.008), albumin (34.2 vs 31.5 g/L; p < 0.001), and prealbumin (0.19 vs 0.16 g/L; p = 0.001) was significantly increased, and the bowel wall thickness (1.09 vs 2.04 mm; p < 0.001) was significantly decreased preoperatively in the chemotherapy group compared with the stenting group. The number of mean harvested lymph nodes was greater in the chemotherapy group than in the stenting group (25.6 vs 21.8; p = 0.04). Laparoscopic surgery was performed more frequently (77.1% vs 40.4%; p < 0.001) and a stoma was created less frequently (10.4% vs 28.8%; p = 0.02) in the chemotherapy group than in the stenting group. LIMITATIONS: This trial was limited by the nonrandomized design and a short follow-up period. CONCLUSIONS: This study suggests that elective surgery following neoadjuvant chemotherapy and colonic stenting is a safe, effective, and well-tolerated treatment approach with a high laparoscopic resection rate and a low stoma rate. See Video Abstract at http://links.lww.com/DCR/B980 . RESULTADOS A CORTO PLAZO DE LA CIRUGA ELECTIVA SEGUIDO DE STENT METLICO AUTOEXPANDIBLE Y QUIMIOTERAPIA NEOADYUVANTE EN PACIENTES CON OBSTRUCCIN POR CNCER DE COLON IZQUIERDO: ANTECEDENTES:La colocación de stents colónicos reduce la morbilidad y la formación de estomas por obstrucción por cáncer de colon izquierdo, y el intervalo prolongado entre la colocación de stents y la cirugía con quimioterapia neoadyuvante administrada podría resultar en una menor tasa de estomas y reducción del tumor.OBJETIVO:Evaluar los resultados a corto plazo de la cirugía electiva después de la colocación de stent en el colon en comparación con la cirugía electiva después de la colocación de stent en el colon y la quimioterapia neoadyuvante en pacientes con obstrucción por cáncer de colon izquierdo.DISEÑO:Estudio prospectivo de cohorte multicéntrico.ENTORNO CLINICO:Este estudio se realizó en 5 centros médicos.PACIENTES:Se incluyeron pacientes (n=100) con obstrucción aguda por cáncer de colon izquierdo que se sometieron a colocación de stent colónico entre diciembre de 2015 y diciembre de 2019.INTERVENCIONES:Los pacientes fueron asignados al grupo de stent solo o quimioterapia.MEDIDAS DE RESULTADO PRINCIPALES:Los resultados primarios medidos fueron la cirugía laparoscópica y la tasa de ostomía.RESULTADOS:De los 100 pacientes que se sometieron a la colocación de stent colónico, 52 fueron asignados al grupo de colocación de stent y 48 al grupo de quimioterapia. No se detectaron diferencias estadísticamente significativas en las complicaciones relacionadas con el stent. Los eventos adversos asociados con la quimioterapia neoadyuvante fueron bien tolerados. Hemoglobina (117,2 g/l vs. 107,6 g/l; p = 0,008), albúmina (34,2 g/l vs. 31,5 g/l; p < 0,001) y prealbúmina (0,19 g/l vs. 0,16 g/l; p = 0,001) aumentaron significativamente y el grosor de la pared intestinal (1,09 mm vs. 2,04 mm; p < 0,001) disminuyó significativamente antes de la operación en el grupo de quimioterapia en comparación con el grupo de colocación de stent. El número medio de ganglios linfáticos extraídos fue mayor en el grupo de quimioterapia que en el grupo de stent (25,6 vs. 21,8; p = 0,04). La cirugía laparoscópica se realizó con mayor frecuencia (77,1 % vs. 40,4 %; p < 0,001) y se creó un estoma con menos frecuencia (10,4 % vs. 28,8 % ; p = 0,02) en el grupo de quimioterapia que en el grupo de colocación de stent.LIMITACIONES:Este ensayo estuvo limitado por el diseño no aleatorio y el corto período de seguimiento.CONCLUSIONES:Este estudio sugiere que la cirugía electiva después de la quimioterapia neoadyuvante y la colocación de stent colónico es un tratamiento seguro, efectivo y bien tolerado, con una alta tasa de resección laparoscópica y una baja tasa de estoma. Consulte Video Resumen en http://links.lww.com/DCR/B980 . (Traducción- Dr. Francisco M. Abarca-Rendon ).
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Neoplasias do Colo , Neoplasias Colorretais , Obstrução Intestinal , Humanos , Terapia Neoadjuvante/efeitos adversos , Estudos Prospectivos , Estudos de Coortes , Neoplasias do Colo/complicações , Neoplasias do Colo/terapia , Neoplasias do Colo/patologia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Stents , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Colorretais/cirurgiaRESUMO
Background: RNA-binding proteins (RBPs) have important roles in orchestrating posttranscriptional regulation and modulating many tumorigenesis events. SERBP1 has been recognized as an important regulator in multiple cancers, while it remains unclear whether SERBP1-regulated gene expression at the transcriptome-wide level is significantly correlated with tumorigenesis. Methods: We overexpressed SERBP1 in HeLa cells and explored whether SERBP1 overexpression (SERBP1-OE) affects the proliferation and apoptosis of HeLa cells. We analyzed the transcriptome-wide gene expression changes and alternative splicing changes mediated by SERBP1-OE using the transcriptome sequencing method (RNA-seq). RT-qPCR was conducted to assay SERBP1-regulated alternative splicing. Results: SERBP1-OE induced the apoptosis of HeLa cells. The downregulated genes were strongly enriched in the cell proliferation and apoptosis pathways according to the GO analysis, including FOS, FOSB, PAK6 and RAB26. The genes undergoing at least one SERBP1-regulated alternative splicing event were enriched in transcriptional regulation, suggesting a mechanism of the regulation of gene expression, and in pyruvate and fatty acid metabolic processes critical for tumorigenesis events. The SERBP1-regulated alternative splicing of ME3, LPIN3, CROT, PDP1, SLC27A1 and ALKBH7 was validated by RT-qPCR analysis. Conclusions: We for the first time demonstrated the cellular function and molecular targets of SERBP1 in HeLa cells at transcriptional and post-transcriptional levels. The SERBP1-regulated gene expression and alternative splicing networks revealed by this study provide important information for exploring the functional roles and regulatory mechanisms of SERBP1 in cancer development and progression.
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Processamento Alternativo , Transcriptoma , Humanos , Processamento Alternativo/genética , Células HeLa , Proliferação de Células/genética , Carcinogênese , Enzimas AlkB/genética , Proteínas Mitocondriais/genéticaRESUMO
Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ_0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ_0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ_0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ_0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ_0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis.
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Neoplasias Colorretais , MicroRNAs , Adenosina/análogos & derivados , Adenosina/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Proteína 4 Homóloga a Disks-Large/genética , Regulação Neoplásica da Expressão Gênica , Glucose , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Via de Pentose Fosfato/genética , RNA Circular/genéticaRESUMO
Anastomotic leakage (AL) is a common complication after intersphincteric resection (ISR). It significantly reduces quality of life and causes great distress to patients. Although traditional drainage (e.g., anal and pelvic catheters) may reduce the impact of AL to some extent, their role in reducing the incidence of AL remains controversial. In this study, we developed a novel drainage technique involving the placement of drainage tubes through the gap between sutures during handsewn anastomosis, to reduce the occurrence of anastomotic leakage. We retrospectively analyzed 34 consecutive patients who underwent intersphincteric resection requiring handsewn anastomosis between February 1, 2017, and January 1, 2021. Patients were classified into the trans-anastomotic drainage tube group (TADT, n = 14) and the non-TADT group (n = 20) based on whether trans-anastomotic tube placement was performed. The incidence of postoperative complications, such as AL, was compared between the two groups, and anal function of patients at 1-year post-ISR was evaluated. Six cases of AL occurred in the non-TADT group, while none occurred in the TADT group; this difference was statistically significant (p=0.031). The TADT group also had a shorter hospital stay (p=0.007). There were no other significant intergroup differences in operation time, blood loss, pain score, anastomotic stenosis, intestinal obstruction, or incidence of wound infection. In the 30 patients (88.2%) evaluated for anal function, there were no significant intergroup differences in stool frequency, urgency, daytime/nocturnal soiling, Wexner incontinence score, or Kirwan grading. Taken together, trans-anastomotic tube placement is a novel drainage method that may reduce AL after ISR requiring handsewn anastomosis and without adversely affecting anal function.
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Cancer models, which are biologically representative of patient tumors, can predict the treatment responses and help determine the most appropriate cancer treatment for individual patients. Here, a point-of-care testing system called acoustically bioprinted patient-derived microtissues (PDMs) that can model cancer invasion and predict treatment response in individual patients with colorectal cancer (CRC), is reported. The PDMs are composed of patient-derived colorectal tumors and healthy organoids which can be precisely arranged by acoustic bioprinting approach for recapulating primary tissue's architecture. Particularly, these tumor organoids can be efficiently generated and can apprehend histological, genomic, and phenotypical characteristics of primary tumors. Consequently, these PDMs allow physiologically relevant in vitro drug (5-fluorouracil) screens, thus predicting the paired patient's responses to chemotherapy. A correlation between organoid invasion speed and normalized spreading speed of the paired patients is further established. It provides a quantitative indicator to help doctors make better decisions on ultimate anus-preserving operation for extremely low CRC patients. Thus, by combing acoustic bioprinting and organoid cultures, this method may open an avenue to establish complex 3D tissue models for precision and personalized medicine.
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Bioimpressão , Neoplasias Colorretais , Acústica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Humanos , Organoides/patologiaRESUMO
Cancer metastasis causes most cancer-related deaths, and modeling cancer invasion holds potential in drug discovery and companion diagnostics. Although 2D cocultures have been developed to study cancer invasion, it is challenging to recreate the 3D cancer invasion of an individual cancer patient. Here, we report an acoustic bioprinting technology that can precisely construct tumor microtissues for modeling cancer invasion in 3D. By using acoustic droplet technology, we can precisely encapsulate cancer associated fibroblasts (CAFs) derived from a colorectal cancer patient into gel droplets and print them into a 3D CAF microtissue. After depositing a tumor organoid derived from the same patient, our 3D bio-printed microtissue can be used to model cancer cell migration and invasion from the tumor organoid to the 3D CAF microtissue. We further used 3D bio-printed microtissues to investigate cancer invasion dynamics as well as their treatment response using time-lapse imaging. Thus, our acoustic 3D bioprinting technology can be widely used for establishing various microtissues for modeling cancer invasion and other diseases, highlighting its potential in personalized treatment.
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Bioimpressão , Neoplasias , Movimento Celular , Técnicas de Cocultura , HumanosRESUMO
Colorectal cancer (CRC) is a common malignancy worldwide, and the gut microbiota and metabolites play an important role in its initiation and progression. In this study, we constructed a mouse model of inflammation-induced colorectal tumors, with fixed doses of azoxymethane/dextran sulfate sodium (AOM/DSS). We found that colorectal tumors only formed in some mice treated with certain concentrations of AOM/DSS (tumor group), whereas other mice did not develop tumors (non-tumor group). 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS)/MS analyses were performed to investigate the microbes and metabolites in the fecal samples. As a result, 1189 operational taxonomic units (OTUs) were obtained from the fecal samples, and the non-tumor group had a relatively higher OTU richness and diversity. Moreover, 53 different microbes were identified at the phylum and genus levels, including Proteobacteria, Cyanobacteria, and Prevotella. Furthermore, four bacterial taxa were obviously enriched in the non-tumor group, according to linear discriminant analysis scores (log10) > 4. The untargeted metabolomics analysis revealed significant differences between the fecal samples and metabolic phenotypes. Further, the heatmaps and volcano plots revealed 53 and 19 dysregulated metabolites between the groups, in positive and negative ion modes, respectively. Styrene degradation and amino sugar-nucleotide sugar metabolism pathways were significantly different in positive and negative ion modes, respectively. Moreover, a correlation analysis between the metabolome and microbiome was further conducted, which revealed the key microbiota and metabolites. In conclusion, we successfully established a tumor model using a certain dose of AOM/DSS and identified the differential intestinal microbiota and characteristic metabolites that might modulate tumorigenesis, thereby providing new concepts for the prevention and treatment of CRC.
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BACKGROUND: Anastomotic leakages (ALs) are one of the most serious complications following gastrointestinal anastomosis. Currently, very few operative measures are available for the prevention of ALs. This pilot study aimed to evaluate the safety and efficacy of tube enterostomy (T-E) for the prevention of ALs in patients with high-risk intestinal anastomosis. METHODS: In this retrospective study, demographic data and postoperative outcomes were compared among patients who received T-E and two historical cohorts: one group that underwent primary anastomosis without T-E (non-T-E group) and another that underwent conventional stoma construction without anastomosis (stoma group). The operative procedures were selected according to a scoring system that quantitatively evaluated risk of Als (Zhongnan score). RESULTS: From March 2017 to March 2020, a total of 45 consecutive patients were enrolled in the T-E group. Among these patients, 53.3% (24/45) were diagnosed with Crohn's disease (CD), and 66.7% (30/45) of them underwent emergency surgery. After propensity score matching, the demographic data were comparable among the three groups. One case of AL (2.2%) occurred in the T-E group, while four cases of ALs (8.9%, 4/45) were found in the non-T-E group (p = 0.13). Tube feeding was provided to 33.3% (15/45) of the T-E patients. Major tube-related complications included one tube dislocation (2.2%) and 3 (6.7%) minor leakages after tube withdrawal (treated conservatively). One death occurred in the stoma group. In the subgroup analysis of CD patients, lower rates of ALs and abdominal abscesses were observed in the T-E group than in the non-T-E and stoma subgroups, but the differences were not significant. CONCLUSIONS: T-E seems to be a safe and feasible operative method for the protection of high-risk intestinal anastomosis, can be reversed and can provide enteral feeding with acceptable tube-related complications. Further studies are needed to validate the role of T-E.
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Fístula Anastomótica , Enterostomia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Humanos , Projetos Piloto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
Background: Pouchitis is the most common long-term complication after ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Ulcerative colitis endoscopic index of severity (UCEIS) and Mayo endoscopic score (MES) are widely used indices to evaluate endoscopic activity. This study aimed to clarify the predictive value of preoperative endoscopic activity on the occurrence of pouchitis after IPAA. Methods: Data of patients with UC who underwent IPAA from January 2008 to January 2020 were collected retrospectively. UCEIS and MES were based on the preoperative colonoscopy findings of two independent endoscopists. Results: A total of 102 patients with a median follow-up of 5 (interquartile range, 2-9) years were included in the study. Among them, 21.6% developed pouchitis. Compared with MES, UCEIS had a stronger correlation with pouchitis disease activity index. UCEIS ≥ 7 had the most significant receiver-operating characteristic (ROC) curve area of 0.747 with a sensitivity of 68.2% and specificity of 81.2% in predicting pouchitis, which outperformed MES of 3 with an ROC area of 0.679 with a sensitivity of 54.5% and specificity of 81.2%. Furthermore, we found that UCEIS ≥ 7 was an independent risk factor for post-IPAA pouchitis [odds ratio (OR), 8.860; 95% CI, 1.969-39.865, p < 0.001] with a higher risk than MES of 3 (OR, 5.200; 95% CI, 1.895-14.273; p = 0.001). Conclusion: Ulcerative colitis endoscopic index of severity performed better in predicting pouchitis after IPAA than MES. Earlier and more frequent postoperative colonoscopic surveillance should be considered in patients with preoperative UCEIS ≥ 7 to detect the occurrence of pouchitis earlier.
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[This retracts the article DOI: 10.3892/ol.2014.2753.].
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Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of CC and therapeutic targets for its treatment.NEW & NOTEWORTHY In this study, we constructed a murine model and identified a novel signaling mechanism involved in the chronic constipation progression. Our findings on the role of miR-128/p38α/M-CSF axis provide new insights into the treatment of chronic constipation.
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Constipação Intestinal/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular Tumoral , Colo/metabolismo , Constipação Intestinal/genética , Feminino , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , MicroRNAs/genética , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Hepatocellular carcinoma (HCC) has high associated morbidity and mortality rates. Although chemical medication represents a primary HCC treatment strategy, low response rates and therapeutic resistance serve to reduce its efficacy. Hence, identifying novel effective drugs is urgently needed, and many researchers have sought to identify new anti-cancer drugs from marine organisms. The marine population is considered a "blue drug bank" of unique anti-cancer compounds with diverse groups of chemical structures. Here, we discuss marine-derived compounds, including PM060184 and bryostatin-1, with demonstrated anti-cancer activity in vitro or in vivo. Based on the marine source (sponges, algae, coral, bacteria, and fungi), we introduce pharmacological parameters, compound-induced cytotoxicity, effects on apoptosis and metastasis, and potential molecular mechanisms. Cumulatively, this review provides insights into anti-HCC research conducted to date in the field of marine natural products and marine-derived compounds, as well as the potential pharmacological mechanisms of these compounds and their status in drug development.
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Antineoplásicos/uso terapêutico , Organismos Aquáticos/química , Produtos Biológicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Bactérias/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Fungos/química , HumanosRESUMO
Cell-based high-throughput screening is a key step in the current disease-based research, drug development, and precision medicine. However, it is challenging to establish a rapid culture and screening platform for rare cells (patient-derived) due to the obvious differences between the traditional 2D cell model and the tumor microenvironment, as well as the lack of a low-consumption screening platform for low numbers of cells. Here, we developed an acoustic drop-assisted superhydrophilic-superhydrophobic microarray platform for the rapid culture and screening of a few cells. By employing hydrophilic and hydrophobic microarrays, we can automatically distribute the cell suspension into uniform droplets, and these cells can spontaneously form compact 3D cell spheroids within 36 h (similar to the microenvironment of tumors in vivo). By using the acoustic droplet ejection device, we can accurately inject a drug solution with a volume of â¼pL to â¼nL into the droplet, and the whole process can be completed within 20 ms (one print). By using three different cell lines (Caco-2, MCF-7, and HeLa) to optimize the platform, the culture and screening of five patients' colon cancer were subsequently realized. Using three conventional chemotherapeutics (5-fluorouracil, cetuximab, and panitumumab) of various concentrations, the best treatment was screened out and compared with the actual treatment effect of the patients, and the results were extremely similar. As a proof-of-concept application, we have proved that our platform can quickly cultivate patient samples and effectively screen the best treatment methods, highlighting its wide application in precision medicine, basic tumor research, and drug development.