Metformin is associated with good tumor response in preoperative concurrent chemoradiotherapy (CCRT) for rectal cancer. This study aims to demonstrate that the timing of metformin is related to the ...tumor response on preoperative CCRT for rectal cancer. From January 2010 to December 2017, 232 patients who underwent curative resection after preoperative CCRT were reviewed. Patients were divided into groups with or without diabetes or metformin. The timing of metformin administration was divided based on before and from initiation of CCRT. Multivariate logistic regression analysis was used to identify predictors for tumor response. Tumor downstaging (p = 0.02) and good response rates of tumor regression grade (TRG) (p = 0.008) were significantly higher in the group administered metformin before CCRT than other groups. In the multivariate analysis, metformin administration before CCRT was a significant factor in predicting tumor downstaging odds ratio (OR) 10.31, 95% confidence interval (CI) 1.76-102.08, p = 0.02 and good TRG (OR 12.55, 95% CI 2.38-80.24, p = 0.004). In patients with rectal cancer who underwent preoperative CCRT, neoadjuvant therapy of metformin before CCRT was significantly associated with good tumor response.
Metastasis and chemoresistance remain major challenges in the clinical treatment of breast cancer. Recent studies show that dysregulated microRNAs (miRNAs) play an important role in metastasis and ...chemoresistance development in breast cancer. Herein, we identified downregulated expression of miR‐708‐3p in breast cancers. In particular, miR‐708‐3p expression was significantly decreased in specimens from breast cancer patients with metastasis compared to that in specimens from patients with no metastasis. Consistent with clinical data, our in vitro data show that miR‐708‐3p was more significantly decreased in invasive breast cancer cell lines. In addition, our data show that inhibition of miR‐708‐3p significantly stimulated breast cancer cell metastasis and induced chemoresistance both in vitro and in vivo. In contrast, overexpression of miR‐708‐3p dramatically inhibited breast cancer cell metastasis and enhanced the sensitivity of breast cancer cells to chemotherapy both in vitro and in vivo. Furthermore, we identified that miR‐708‐3p inhibits breast cancer cell epithelial‐to‐mesenchymal transition (EMT) by directly targeting EMT activators, including ZEB1, CDH2 and vimentin. Taken together, our findings suggest that miR‐708‐3p acts as a cancer suppressor miRNA and carries out its anticancer function by inhibiting EMT in breast cancer. In addition, our findings suggest that restoration of miR‐708‐3p may be a novel strategy for inhibiting breast cancer metastasis and overcoming the chemoresistance of breast cancer cells.
Decreased expression of miR‐708‐3p was correlated with metastasis in breast cancer. Overexpression of miR‐708‐3p inhibits breast cancer cell metastasis and enhances chemosensitivity of breast cancer cells by inhibiting EMT.
Non-operative treatment is the mainstay of colonic diverticulitis, but some patients require surgery due to non-operative treatment failure. This study aims to identify risk factors for the failure ...of non-operative treatment of colonic diverticulitis. From January 2011 to December 2020, we retrospectively reviewed 2362 patients with non-operative treatment for first-attack acute diverticulitis. Patients were categorized into non-operative treatment success or failure groups. Clinical characteristics and serum inflammatory markers were analyzed by multivariable logistic regression to determine risk factors for non-operative treatment failure of colonic diverticulitis. Overall, 2.2% (n = 50) of patients underwent delayed surgery within 30 days (median 4.0 3.0; 8.0) due to non-operative treatment failure. Multivariable logistic regression identified that platelet to lymphocyte ratio (odds ratio OR, 4.2; 95% confidence interval CI, 0.05-0.13; p < 0.001), diabetes mellitus (OR, 2.2; 95% CI, 0.01-0.09; p = 0.025), left-sided colonic diverticulitis (OR, 4.1; 95% CI, 0.04-0.13; p < 0.001), and modified Hinchey classification (OR, 6.2; 95% CI, 0.09-0.17; p < 0.001) were risk factors for non-operative treatment failure. Platelet to lymphocyte ratio (PLR) is a potential risk factor for the non-operative treatment failure of acute first-attack colonic diverticulitis. Therefore, patients with higher PLR during non-operative treatment should be monitored with special caution.
Chemotherapy-induced cognitive impairment (CICI) is increasingly recognized as a major unwanted side effect of an otherwise highly valuable life-saving technology. In part, this awareness is a result ...of increased cancer survival rates following chemotherapy. Altered hippocampal neurogenesis may play a role in mediating CICI. In particular, zinc could act as a key regulator of this process. To test this hypothesis, we administered paclitaxel (Px) to male C57BL/6 mice for set time periods and then evaluated the effects of Px treatment on hippocampal neurogenesis and vesicular zinc. We found that vesicular zinc levels and expression of zinc transporter 3 (ZnT3) were reduced in Px-treated mice, compared to vehicle-treated mice. Moreover, Px-treated mice demonstrated a significant decrease in the number of neuroblasts present. However, no difference in the number of progenitor cells were observed. In addition, zinc supplementation by treatment with ZnCl
ameliorated the Px-induced decrease in hippocampal neurogenesis and cognitive impairment. These results suggest that via disruption of vesicular zinc stores in hippocampal mossy fiber terminals, chemotherapy may impinge upon one or more of the sequential stages involved in the maturation of new neurons derived via adult neurogenesis and thereby leads to the progressive cognitive decline associated with CICI.
infections are a major cause of gastrointestinal disorders, including gastric ulcers, gastritis, and gastric cancer. Triple therapy, using two antibiotics and a proton pump inhibitor, is recommended ...for the treatment of
infections. However, antibiotic resistance in
is an emerging issue. Bamboo salt, a traditional Korean salt made by baking solar sea salt in bamboo barrels, can ameliorate the symptoms of various gastrointestinal diseases. Herein, we compared the anti-
activity of triple therapy (clarithromycin, metronidazole, and omeprazole), solar salt, and bamboo salt in vivo as a preliminary study. Four-week-old C57BL/6 male mice were inoculated for eight weeks with the
Sydney Strain 1 (SS-1) and orally administered triple therapy drugs and salts for five days. The transcript levels of the
-expressed gene
and inflammatory cytokines
and
significantly decreased in the bamboo salt treated mice than those in the
-infected control group. This effect was further enhanced by using triple therapy and bamboo salt together. Solar salt caused modest inhibition of
-induced inflammation. We also demonstrated the synergistic effects of bamboo salt and triple therapy against
. Thus, bamboo salt may be a potential candidate agent against the treatment of
-associated gastritis.
The purpose of this cross-sectional study was to compare the independent contributions of medical comorbidity, cognition, and age on patient-reported outcomes in Parkinson's disease (PD).
572 PD ...patients completed the Patient-Reported Outcome Measurement Information System (PROMIS®)-29 v2.0 Profile (physical function, anxiety, depression, fatigue, sleep disturbance, satisfaction with participation in social roles, pain interference) and PROMIS Global Health (mental health and physical health) scales. Comorbidity was measured with the Cumulative Illness Rating Scale–Geriatric (CIRS-G) and cognition with the Montreal Cognitive Assessment (MoCA). Multiple regression models examined the 9 PROMIS measures as predicted by comorbidity, cognition, and age, adjusting for demographic and clinical characteristics (UPDRS and disease duration).
Comorbidity was associated with poorer outcomes in all nine PROMIS domains. Cognition was associated with two of nine domains: physical function and anxiety. Age was associated with five domains: anxiety, depression, sleep disturbance, satisfaction with participation in social roles, and global mental health. Comorbidity showed greater effects on all nine domains than cognition or age (higher standardized beta coefficients).
Medical comorbidity, cognition, and age have different impacts on patient-reported outcomes in PD. Medical comorbidity has a greater impact than either cognition or age on a range of patient-reported physical and mental health domains. Medical comorbidity is an important contributor to the patient's perspective of their physical and mental health.
•Comorbidity, cognition, and age have different impacts on nine domains of patient-reported health outcomes.•Higher comorbidity was associated with poorer patient-reported health outcomes, even when controlling for disease severity.•Comorbidity had stronger effects than cognition and age on all of nine patient-reported health outcomes.•We suggest an increased awareness of the impact of comorbidity among PD patients during clinical visits.
Most known osteoporosis medicines are effective for bone resorption, and so there is an increasing demand for medicines that stimulate bone formation. Watercress (N. officinale R. Br.) is widely used ...as a salad green and herbal remedy. This study analyzed a watercress extract using ultra-performance liquid chromatography/mass spectrometry, and identified a rutin as one of its major constituents. Osteogenic-related assays were used to compare the effects of watercress containing rutin (WCR) and rutin alone on the proliferation and differentiation of human osteoblast-like MG-63 cells. The reported data are expressed as percentages relative to the control value (medium alone; assigned as 100%). WCR increased cell proliferation to $125.0{\pm}4.0%$ ($mean{\pm}SD$), as assessed using a cell viability assay, and increased the activity of alkaline phosphatase, an early differentiation marker, to $222.3{\pm}33.8%$. In addition, WCR increased the expression of collagen type I, another early differentiation marker, to $149.2{\pm}2.8%$, and increased the degree of mineralization, a marker of the late process of differentiation, to $122.9{\pm}3.9%$. Rutin alone also increased the activity of ALP (to $154.4{\pm}12.2%$), the expression of collagen type I (to $126.6{\pm}6.2%$), and the degree of mineralization (to $112.3{\pm}5.0%$). Daidzein, which is reported to stimulate bone formation, was used as a positive control; the effects of WCR on proliferation and differentiation were significantly greater than those of daidzein. These results indicate that WCR and rutin can both induce bone formation via the differentiation of MG-63 cells. This is the first study demonstrating the effectiveness of either WCR or rutin as an osteoblast stimulant.
By observing temporary and permanent changes in threshold voltage (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {T}} </tex-math></inline-formula>) due to the application of unipolar/bipolar ...stress, it was confirmed that the trap-carrier interaction speed is the cause of failure of the ferroelectric transistor as a memory. As the polarization switching occurs, carriers are trapped in the ferroelectric/interfacial layer (FE/IL), and the hole trap is limited compared to the electron trap due to the slow interaction. IL degrades under bipolar stress due to the high electric field during polarization switching, leading to the acceleration of hole trapping, which has a strong impact on the memory window.
Recent studies show that dysregulated miRNAs play an important role in breast cancer initiation and progression. Here, we identified upregulated expression of miR-1307-3p in breast cancer tissues and ...that increased level of miR-1307-3p was closely correlated with lower survival rate in breast cancer patients. Consistent with clinical data, our
data show that expression level of miR-1307-3p was significantly increased in breast cancer cell lines compared to human mammary epithelial cell line MCF10A. Overexpression of miR-1307-3p in MCF10A stimulated cell proliferation and caused their growth in soft agar and tumor formation in nude mice. In contrast, inhibition of miR-1307-3p suppressed breast cancer cell proliferation and their growth in soft agar and inhibited tumor formation in nude mice. Further, we identified that miR-1307-3p plays its oncogenic role through targeting SET and MYND domain-containing 4 (SMYD4) expression in breast cancer. Taken together, our findings suggest that miR-1307-3p is a oncogenic miRNA that significantly contributes to breast cancer development and progression, and inhibition of miR-1307-3p may be a novel strategy for inhibits breast cancer initiation and progression.
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