Early oral hydration on demand in postanesthesia care unit effectively relieves postoperative thirst in patients after gynecological laparoscopy: a prospective randomized controlled trial.

BACKGROUND: Postoperative thirst is one of the most intense, common and easily ignored subjective discomforts in patients after gynecological surgery. This study aimed to investigate whether early oral hydration on demand in the postanesthesia care unit (PACU) after gynecological laparoscopy under general anesthesia can appease postoperative thirst and increase patient comfort. METHODS: Participants were randomized into the intervention and control groups. Patients in the intervention group were allowed to achieve early oral hydration on demand in the PACU if they were evaluated as fully conscious, with stable vital signs, grade 5 muscle strength, and well-recovered cough and swallowing reflex. However, the total amount of water intake throughout the entire study should not exceed 0.5mL/kg. During the study, the frequency of water intake, the total amount of water intake and adverse events were accurately recorded. The control group was managed according to the routine procedures and began to drink water 2 h after anesthesia. The intensity of thirst and subjective comfort in patients were assessed using the visual analog scale (VAS) when they entered and left the PACU. RESULTS: No statistically significant differences were identified in age, height, weight, body mass index, pre-operative fasting time, duration of surgery, intraoperative fluid intake, intraoperative blood loss, intraoperative urine volume, and thirst intensity and subjective comfort scores between the groups before intervention (P > 0.05). After intervention, the VAS score for thirst intensity in the intervention group significantly decreased (P < 0.05), and the VAS score for subjective comfort in the intervention group significantly increased (P < 0.05). No adverse events were detected in both groups during the entire study. CONCLUSION: Early oral hydration on demand in the PACU can safely and effectively relieve postoperative thirst in patients, and improve patient comfort after gynecological laparoscopy. TRIAL REGISTRATION: This single-center, prospective, randomized controlled trial was registered at the Chinese Clinical Trial Center on April 27, 2023. The registration number of this study is ChiCTR2300070985.

Contribution of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 to Upper Tract Urothelial Cancer Risk in Taiwan.

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.

Upconverting Ultra-Thin Bi2O2CO3 Nanosheets for Synergistic Photodynamic Therapy and Radiotherapy.

Synergistic therapy has become the major therapeutic method for malignant tumors in clinical. Photodynamic therapy (PDT) and radiotherapy (RT) always combine together because of their identical anti-tumor mechanisms, that is reactive oxygen species are generated by the use of radiosensitizers after irradiation by X-ray to efficiently kill cancer cells, PDT also follows similar mechanism. Full exposure of energy-absorbing species in nanomaterials to X-ray or near-infrared light irradiation makes the energy interchange between nanomaterials and surrounding H2O or dissolved oxygen easier, however, it remains challenging. Herein, an ultrathin two-dimensional (2D) nanosheet (NS) is developed, Bi2O2CO3, doped with lanthanide ions to give out upconversion luminescence, where the high Z elements Bi, Yb, and Er promote the radio-sensitizing effect. To the surprise, lanthanide activator ions gave out completely different luminescence properties compared with traditional upconversion nanoparticles. Less dopant of Er ions in nanosheets lattice resulted in brighter red emission, which provides more efficient PDT. Under RT/PDT combined treatment, NS shows a good tumor growth-inhibiting effect. In addition, synergistic therapy requires lower radiation dose than conventional radiotherapy and lower light power than single photodynamic therapy, thus greatly reducing radiation damage caused by RT and thermal damage caused by PDT.

Landscape genomics reveals genetic signals of environmental adaptation of African wild eggplants.

Crop wild relatives (CWR) provide a valuable resource for improving crops. They possess desirable traits that confer resilience to various environmental stresses. To fully utilize crop wild relatives in breeding and conservation programs, it is important to understand the genetic basis of their adaptation. Landscape genomics associates environments with genomic variation and allows for examining the genetic basis of adaptation. Our study examined the differences in allele frequency of 15,416 single nucleotide polymorphisms (SNPs) generated through genotyping by sequencing approach among 153 accessions of 15 wild eggplant relatives and two cultivated species from Africa, the principal hotspot of these wild relatives. We also explored the correlation between these variations and the bioclimatic and soil conditions at their collection sites, providing a comprehensive understanding of the genetic signals of environmental adaptation in African wild eggplant. Redundancy analysis (RDA) results showed that the environmental variation explained 6% while the geographical distances among the collection sites explained 15% of the genomic variation in the eggplant wild relative populations when controlling for population structure. Our findings indicate that even though environmental factors are not the main driver of selection in eggplant wild relatives, it is influential in shaping the genomic variation over time. The selected environmental variables and candidate SNPs effectively revealed grouping patterns according to the environmental characteristics of sampling sites. Using four genotype-environment association methods, we detected 396 candidate SNPs (2.5% of the initial SNPs) associated with eight environmental factors. Some of these SNPs signal genes involved in pathways that help adapt to environmental stresses such as drought, heat, cold, salinity, pests, and diseases. These candidate SNPs will be useful for marker-assisted improvement and characterizing the germplasm of this crop for developing climate-resilient eggplant varieties. The study provides a model for applying landscape genomics to other crops' wild relatives.

Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

The effects of diabetes, hypertension and subsequent health control behavior on the survival of a Taiwan cohort aged over 50 years.

Purpose: This study used the Taiwan Longitudinal Study in Aging from 1996 to 2011 to investigate the effects of diabetes, hypertension, and healthy living behaviors of those aged over 50 years on the survival status in Taiwan. Methods: Among the 5,131 participants aged 50 years and above in the 1996 survey were included in this study. Cox's proportional hazards model was used to examine the incidence of diabetes, hypertension, and related mortality risk in those aged over 50 years. Results: After adjusting for age, gender, education level, diabetes, hypertension, health behavior, and leisure activity, results from the Cox model show that the elderly without diabetes have a lower mortality risk than those with diabetes. Regular exercise was associated with a lower risk of mortality. The hazard ratios of elderly with regular exercise were 0.78 (95 % CI: 0.64-0.96) for two times a week or less, 0.81 (95 % CI: 0.69-0.96) for 3-5 times a week, and 0.84 (95 % CI: 0.77-0.93) for 6 + times a week, respectively. On the other hand, leisure activity positively reduces mortality risk. For example, the hazard ratios of the elderly with watching TV and reading were 0.63 (95 % CI: 0.55-0.72) and 0.80 (95 % CI: 0.72-0.89), respectively. Moreover, smoking can increase mortality risk 23 % whether the elderly are with diabetes or hypertension or not. Conclusions: Regarding preventing and controlling chronic diseases in the future, continuously encouraging improvement in health behavior and engaging in leisure activities for the middle-aged and over should be considered essential markers.

The benefits of leisure activities on healthy life expectancy for older people with diabetes.

PURPOSE: The purpose of this study is to examine whether leisure activities can help reduce years lived with disability and increase healthy life expectancy of diabetics aged 50 years and above. METHODS: Analysis was based on five waves of follow-up survey data (Taiwan Longitudinal Study of Aging, TLSA) from 1996 to 2011. A total of 5131 participants aged 50 years and above in 1996 were included in the analysis, and gender, leisure activity participation, and diabetes mellitus were used as primary variables to examine the variation trend in health status in the participants. The health status in the various waves of surveys was measured using the activities of daily living scale, and nondisabled was defined as healthy. A multivariate logistic regression model was used to calculate the life expectancy (LE) and healthy life expectancy (HLE) of the people aged 50 years and above. RESULTS: The diabetes older people with a high frequency of leisure activities have longer HLE than those with lower activity frequency. Using 50-year-old diabetic women as an example, the LE (HLE) of those with six or more leisure activities and those with three or fewer leisure activities was 30.40 (25.34) and 24.90 (20.87), respectively. The LE (HLE) of men with the same conditions was 24.79 (22.68) and 20.30 (18.45), respectively. CONCLUSIONS: This study used life expectancy and healthy life expectancy as markers to evaluate health benefits and provided evidence that leisure activities can help extend the life span and maintain the health status of middle-aged and older diabetics.

Associations of Matrix Metalloproteinase-8 Genotypes to Renal Cell Carcinoma in Taiwan.

BACKGROUND/AIM: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aimed to elucidate the role of MMP-8 genotypes in RCC susceptibility. MATERIALS AND METHODS: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, sex, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed. RESULTS: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, sex, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes. CONCLUSION: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC.

A single-agent fusion of human IL-2 and anti-IL-2 antibody that selectively expands regulatory T cells.

The occurrence of many autoimmune diseases takes root on the disrupted balance among Treg cells, Teff cells, etc. Low-dose interleukin-2 (IL-2) cytokine demonstrates promising clinical efficacy in the expansion of Treg cells and the treatment of autoimmune diseases. However, its clinical application is hindered by the small therapeutic index and short half-life. Previous studies have shown that non-covalent complex of human IL-2 and anti-IL-2 antibody biases cytokine activity towards Treg cells and extends IL-2's half-life. The clinical translation of such complex is non-trivial. In this study, we discover an anti-human IL-2 antibody and engineer a covalently-linked single-agent fusion of human IL-2 and its antibody that selectively expands Treg cells and exhibits superior disease control activity in animal models of ulcerative colitis and systemic lupus erythematosus, with proper safety profile and good developability. These studies pave the road for its clinical development in diverse autoimmune diseases.

Escherichia coli-Induced cGLIS3-Mediated Stress Granules Activate the NF-κB Pathway to Promote Intrahepatic Cholangiocarcinoma Progression.

Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.

Glucose-lightened upconversion nanoprobes for accurate cellular-discrimination based on Warburg effect.

Accurate cellular-recognition based disease therapy is of significance for precision medicine. However, except of specific antibody-coupling strategy, very few probes have been reported to efficiently discriminate normal cells and lesion cells through cellular microenvironment. Herein, we proposed a glucose selectively-lightened upconversion nanoprobe to recognize cancer cells from a pile of normal cells based on Warburg effect, that indicated a heightened demand for glucose intake for cancer cells. The nanoprobes were constructed by mesoporous silica-coated upconversion nanoparticles (UCNP@mSiO2) with the crucial incorporation of a glucose-responsive modality, benzoboric acid (BA)-modified fluorescein molecules (FITC-BA). In cancer cells, the presence of elevated glucose concentrations triggered the transformation of FITC-BA to FITC-Glucose to recover nanoprobes' luminescence, however, the nanoprobes exhibited a shielded luminescent effect in healthy cells. To validate the hypothesis of accurate cellular-discrimination, a photodynamic therapy modality, riboflavin, with a specific ratio were also loaded into above UCNP@mSiO2 nanoprobes for effective production of reactive oxygen species to kill cells. It was found that 97.8% of cancer cells were cleaned up, but normal cells retained a nearly 100% viability after 10 min laser illumination. By leveraging the metabolic disparity from Warburg effect, the nanoprobes offer a highly accurate cellular discrimination, and significantly mitigate "off-target" damage commonly associated with conventional therapies.

Uterine cancer among Asian Americans - Disparities & clinical characteristics.

OBJECTIVE: To evaluate the patterns and trends of uterine cancer among Asian subgroups living in the U.S. METHODS: Data were obtained from United States Cancer Statistics (2001-2017), National Cancer Database (2004-2015), and World Population Review (2023). SEER*Stat version 8.3.9.2, Joinpoint regression program 4.9.0.0, and SAS v 9.4 were employed for statistical analysis. RESULTS: Based on data from 778,891 women in the United States Cancer Statistics database, Asians had a 3.4-fold higher rate of incident uterine cancer compared to White populations (2.14% vs. 0.63%; p < 0.001). Using the National Cancer Database, 7,641 Asian women from six subgroups were analyzed: Filipino, Korean, Indian/Pakistani, Vietnamese, Chinese, and Japanese. Indian and Pakistani women had the greatest increase in the proportion of cancer diagnoses (5.0% to 14.4%; p = 0.0003). Additionally, Indian and Pakistani patients had higher comorbidity scores while Koreans had the lowest (22.7% vs. 10.7%, p < 0.0001). Regarding stage of disease, 25.3% of Filipinos presented with advanced stage disease compared to 19.2% of Indians and Pakistanis (p = 0.0001). Furthermore, Filipinos had the highest proportion of non-endometrioid cancers at 18.4% compared to other subgroups (p = 0.0003). Using the World Population Review, female obesity was highest in Pakistan (8.6%) and the Philippines (7.5%) and lowest in Vietnam (2.6%). CONCLUSION: Uterine cancer incidence increased at higher rates among Asians compared to White populations. Specifically, Indian and Pakistani uterine cancer patients were more likely to have higher comorbidity rates and Filipino patients had more advanced stage cancer with non-endometrioid histologies than other Asian subgroups. Further research is warranted to better understand these trends.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

Predictive Value of Nutritional Risk for All-Cause Death and Functional Outcomes in Chinese Elderly Patients with Acute Stroke: A 3-Year Follow-Up Study.

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.

Impacts of Matrix Metalloproteinase 9 Genotypes on Renal Cell Carcinoma.

BACKGROUND/AIM: The expression of matrix metalloproteinase 9 (MMP9) is elevated in various renal diseases, including renal cell carcinoma. However, the role of MMP9 genotype in this context remains unclear. This study aimed to investigate the association between MMP9 promoter rs3918242 genotypes and the risk of renal cell carcinoma. MATERIALS AND METHODS: The MMP9 rs3918242 genotypes of 118 patients with renal cell carcinoma and 590 healthy subjects were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The results indicated that individuals carrying the CT or TT genotype of MMP9 rs3918242 did not exhibit an increased risk of renal cell carcinoma compared to wild-type CC carriers (odds ratio=1.20 and 2.68, 95% confidence interval=0.75-1.92 and 0.89-8.03; p=0.5270 and 0.1420, respectively). However, individuals with the CT and TT genotypes had a higher prevalence of renal cell carcinoma than those with the CC genotype when they also had hypertension (p=0.0010), diabetes (p=0.0010), or a family history of cancer (p<0.00001). No correlation was observed between MMP9 rs3918242 genotypic distribution and age (60 years or younger vs. older than 60 years) or sex (both p>0.05). Additionally, no correlation was found between MMP9 rs3918242 genotype and the risk of renal cell carcinoma in individuals with smoking or alcohol consumption habits. CONCLUSION: Carrying the T allele for MMP9 rs3918242 may predict a higher risk of renal cell carcinoma among individuals diagnosed with hypertension, diabetes, or with a family history of cancer.

A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is characterized by its dense fibrotic microenvironment and highly malignant nature, which are associated with chemotherapy resistance and very poor prognosis. Although circRNAs have emerged as important regulators in cancer biology, their role in ICC remains largely unclear. Herein, a circular RNA, cPKM is identified, which is upregulated in ICC and associated with poor prognosis. Silencing cPKM in ICC cells reduces TGFB1 release and stromal fibrosis, inhibits STMN1 expression, and suppresses ICC growth and metastasis, moreover, it also leads to overcoming paclitaxel resistance. This is regulated by the interactions of cPKM with miR-199a-5p or IGF2BP2 and by the ability of cPKM to stabilize STMN1/TGFB1 mRNA. Based on these findings, a Trojan horse nanotherapy strategy with co-loading of siRNA against cPKM (si-cPKM) and paclitaxel (PTX) is developed. The siRNA/PTX co-loaded nanosystem (Trojan horse) efficiently penetrates tumor tissues, releases si-cPKM and paclitaxel (soldiers), promotes paclitaxel sensitization, and suppresses ICC proliferation and metastasis in vivo. Furthermore, it alleviates the fibrosis of ICC tumor stroma and reopens collapsed tumor vessels (opening the gates), thus enhancing the efficacy of the standard chemotherapy regimen (main force). This novel nanotherapy provides a promising new strategy for ICC treatment.

Multi-target responsive nanoprobe with cellular-level accuracy for spatiotemporally selective photodynamic therapy.

Photodynamic therapy is known for its non-invasiveness to significantly reduce undesired side effects on patients. However, the infiltration and invasiveness of tumor growth are still beyond the specificity of traditional light-controlled photodynamic therapy (PDT), which lacks cellular-level accuracy to tumor cells, possibly leading to "off-target" damage to healthy tissues such as the skin or immune cells infiltrated. Here, upconversion nanoparticles (UCNPs) were co-encapsulated with manganese dioxide (MnO2) by amphiphilic polymers poly(styrene-co-methyl acrylate) (PSMA) and further coated with photosensitizer (riboflavin)-loaded mesoporous silica (C@S/V). The C@S/V nanoprobes exhibited shielded upconversion luminescence in normal conditions (pH 7.4, no hydroperoxide (H2O2)) under 980-nm irradiation and thus minimal reactive oxygen production from riboflavin. However, the excess H2O2 (1 mM) and acidic environment (pH 5.5) could decompose the MnO2 within the C@S/V, resulting in remarkable enhancement of upconversion luminescence and a favorable hypoxia-relieving condition for PDT, providing a spatiotemporal signal for therapy initiation. The C@S/V nanoprobes were applied to the co-culture of normal cells (HEK293) and pancreatic cancer cells (Panc02) and performed a selective killing on Panc02 under the 980-nm irradiation. By using the "double-safety" strategy, a responsive C@S/V nanoprobe was designed by the selective activation of acidic and H2O2-rich conditions and 980-nm irradiation for spatiotemporally selective photodynamic therapy with cellular-level accuracy.

MicroRNA-363-3p inhibits colorectal cancer progression by targeting interferon-induced transmembrane protein 1.

BACKGROUND: The molecular mechanisms of colorectal cancer development and progression are far from being elucidated. AIM: To investigate the role of microRNA-363-3p (miR-363-3p) in the progression of colorectal cancer. METHODS: Real-time polymerase chain reaction was performed to detect miRNA expression in human colorectal cancer tissues and paired normal colorectal tissues. PITA 6 was utilized to predict the targets of miR-363-3p. Dual-luciferase reporter system was used to validate the target of miR-363-3p. Plate colony formation assay and wound-healing assay were performed to evaluate cancer cells' clonogenic survival ability and migration ability, respectively. Cell proliferation was examined by cell counting kit-8 assay. Immunohistochemical staining was used to determine the expression level of interferon-induced transmembrane protein 1 (IFITM1) in colorectal cancer tissues and adjacent tissues. The TCGA and GTEx databases were used to compare the expression levels of IFITM1 mRNA in colorectal cancer tissues and normal colorectal tissues and analyze the correlation between the expression levels of IFITM1 mRNA and overall survival and disease-free survival of patients. A colorectal cancer cell line with a deficiency of IFITM1 was constructed, and the regulation effect of IFITM1 on the clonogenic growth of colorectal cancer cells was clarified. RESULTS: MiR-363-3p was decreased in colorectal cancer tissues compared to normal colorectal tissues. IFITM1 was characterized as a direct target of miR-363-3p. Overexpression of miR-363-3p led to decreased clonogenic survival, proliferation, and migration of colorectal cancer cells, which could be reversed by forced IFITM1 expression. CONCLUSION: MiR-363-3p can constrain clonogenic survival, proliferation, and migration of colorectal cancer cells via targeting IFITM1.