Availability and stability of palliative care for family members of terminally ill patients in an integrated model of health and social care.

BACKGROUND: Palliative care and the integration of health and social care have gradually become the key direction of development to address the aging of the population and the growing burden of multimorbidity at the end of life in the elderly. AIMS: To explore the benefits/effectiveness of the availability and stability of palliative care for family members of terminally ill patients in an integrated institution for health and social care. METHODS: This prospective observational study was conducted at an integrated institution for health and social care. 230 patients with terminal illness who received palliative care and their family members were included. Questionnaires and scales were administered to the family members of patients during the palliative care process, including quality-of-life (SF-8), family burden (FBSD, CBI), anxiety (HAMA), and distress (DT). We used paired t-tests and correlation analyses to analyze the data pertaining to our research questions. RESULTS: In the integrated institution for health and social care, palliative care can effectively improve quality of life, reduce the family's burden and relieve psychological impact for family members of terminally ill patients. Palliative care was an independent influencing factor on the quality of life, family burden, and psychosocial status. Independently of patient-related and family-related factors, the results are stable and widely applicable. CONCLUSION: The findings underline the availability and stability of palliative care and the popularization of an integrated service model of health and social care for elder adults.

CXCL10 mediates CD8+ T cells to facilitate vessel normalization and improve the efficacy of cetuximab combined with PD-1 checkpoint inhibitors in colorectal cancer.

The immunotherapy and anti-EGFR targeted treatment occupying a pivotal position in colorectal cancer (CRC), is still limited to a group of patients who display specific molecular alterations and inevitably escape from resistance, further studies are still needed in colorectal cancer. We found that chemokine ligand 10 (CXCL10) expression correlates with intratumoral CD8+ T cell infiltration and reprograms tumor vasculatures in colorectal cancer. CXCL10 overexpression not only suppressed tumor growth but also increased CD8+ T cell infiltration and induced tumor vascular normalization in vivo. Additionally, the growth inhibition and tumor vascular normalization induced by CXCL10 can be reversed by the depletion of CD8+ T cells in vivo. Mechanically, CXCL10 interacts with VCAN to mediate tumor vascular normalization. The VCAN expression correlated inversely with the expression of CXCL10 and the infiltration of CD8+ T cells in CRC. Elevated CXCL10 expression sensitized colorectal cancer cells to cetuximab/anti-PD1 combination therapy compared with cetuximab or anti-PD1 alone. We propose that CXCL10 could be used to increase the anti-EGFR therapy and immunotherapy effect, targeting both tumor vessels and immune cells in colorectal cancer.

Three Neolignan Glycosides from the Root of Nothopanax davidii.

Three neolignan glycosides, including a new compound (7S,8R)-dihydro-3'-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1'-benzofuranpropanol-9-O-ß-D-xylopyranoside (1), were isolated from the root of Nothopanax davidii. Their structures were determined by extensive spectroscopic analyses, particularly NMR, HR-ESI-MS, and ECD experiments, and the absolute configuration of 2 was first definitively determined. The anti-tumor activity was assessed on four tumor cells by MTT assay, the anti-inflammatory activity was determined by inhibition of NO production in LPS reduced RAW264.7 cells, and the interaction with iNOS was predicted by molecular docking. At the dose of 100 µM, the three neolignan glycosides showed no cytotoxic activity against HepG2, HCT116, HeLa and A549 human tumor cells, but significantly inhibited LPS induced NO generation in RAW264.7 cells with inhibition rates of 31.53 %, 23.95 %, and 20.79 %, respectively, showing weak anti-inflammatory activity, possibly due to their binding to key residues of iNOs involved in inhibitor binding.

circEXOC6B interacting with RRAGB, an mTORC1 activator, inhibits the progression of colorectal cancer by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop.

BACKGROUND: In recent years, an increasing number of studies have indicated that circular RNA plays crucial roles in regulating tumor development and chemoresistance. Using two high-throughput RNA sequence datasets, we previously found that circEXOC6B was downregulated in colon cancer. However, its role and mechanism in colorectal cancer (CRC) remained unknown. METHODS: Real-time quantitative PCR was used to examine the expression of circEXOC6B in CRC tissues. In vivo and in vitro functional experiments were performed to determine the suppressor role of circEXOC6B in CRC progression. RNA pull-down, mass spectrometry, RNA-binding protein immunoprecipitation, co-immunoprecipitation, fluorescence in situ hybridization, and immunofluorescence were applied to investigate the possible mechanisms connecting circEXOC6B to CRC growth and 5-fluorouracil-induced apoptosis. Chromatin immunoprecipitation, dual-luciferase assay, western blot, and immunohistochemistry were used to explore the mechanisms underlying the HIF1A regulation of RRAGB transcription. RESULTS: circEXOC6B was downregulated in CRC tissues, and its lower expression was associated with poor prognosis of patients. Functional experiments showed that circEXOC6B inhibited growth and increased the 5-fluorouracil-induced apoptosis of CRC cells in vitro and in vivo. Mechanistically, circEXOC6B inhibited the heterodimer formation of RRAGB by binding to it, thereby suppressing the mTORC1 pathway and HIF1A level. In addition, HIF1A upregulated the transcription of RRAGB by binding to its promoter region. Altogether, the results demonstrated that a HIF1A-RRAGB-mTORC1 positive feedback loop drives tumor progression in CRC, which could be interrupted by circEXOC6B. CONCLUSIONS: circEXOC6B inhibits the progression of CRC and enhances the chemosensitivity of CRC cells to 5-fluorouracil by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop. circEXOC6B is a possible therapeutic target for CRC treatment.

Inflammatory markers and incident depression: Evidence in a population-based prospective study.

The association between pro-inflammatory cytokines and depression is widely acknowledged. However, longitudinal data that show they lead to depression are few. In a community-based sample of older individuals (n = 2761, ages = 55-98 y) in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the associations between inflammatory markers (CRP, IL6, TNFα, and inflammation risk score) and depression (defined as the presence of depressive symptoms, depression history or treatment). Cross-sectional analysis showed that CRP, IL-6 and TNFα were significantly associated with depression at baseline. Longitudinal analysis controlling for a host of potentially confounding risk factors and initial depression revealed that IL-6, TNFα, and inflammation risk score were associated with elevated risk of depression at follow-ups. However, there was no significant association between CRP and subsequent depression after adjusting for sociodemographic, lifestyles and inflammatory medical condition variables. In summary, this prospective study shows that inflammation predicts depression in older adults, and suggests that the heterogeneous findings among studies may be due to differences in study population characteristics, depression, inflammatory markers, and the extent of adjusting for confounders.

Effect of Intensive Psychological Nursing Intervention on HAMD and SF-36 Scores in Patients with Severe Liver Cancer in ICU.

The aim of the study was to explore the effect of intensive psychological nursing intervention on HAMD and SF-36 scores in patients with severe liver cancer in intensive care unit (ICU). 134 critically ill patients with liver cancer in ICU who underwent resection of primary liver cancer from July 2019 to November 2021 were selected. The patients were randomly divided into control group and study group. The patients in the control group received routine nursing. The patients in the study group received intensive psychological nursing intervention on the basis of routine nursing. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the MOS 36-item short-form health survey (SF-36) scores before and after nursing were compared between the two groups. The satisfaction of the two groups of patients with nursing was counted. The HAMA, HAMD, and SF-36 scores of patients receiving intensive psychological nursing intervention were significantly better than those receiving routine nursing. The nursing satisfaction of patients receiving intensive psychological nursing intervention was significantly higher than that of patients receiving routine nursing. Intensive psychological nursing intervention for patients with severe liver cancer in ICU can significantly reduce HAMD, improve SF-36 score, and patient nursing satisfaction. It is worthy of wide clinical promotion.

Malnutrition Risk and Kidney Function and Decline in Community-Dwelling Older Adults.

OBJECTIVES: The association of malnutrition with chronic kidney disease (CKD) is well established. However, there is a paucity of studies of the effect of malnutrition risk (MR) on kidney function decline among older persons who do not have end-stage or dialyzable CKD. This study aimed to examine the association between MR status and kidney function, and future risks of kidney function decline and CKD progression in community-dwelling older adults. DESIGN AND METHODS: Nutrition Screening Initiative's DETERMINE Your Nutritional Health Checklist and estimated glomerular filtration rate (eGFR) were assessed at baseline among 5,122 participants free of end-stage renal failure or dialyzed CKD in the Singapore Longitudinal Aging Studies (SLAS-1 and SLAS-2). Follow-up eGFR was assessed in a subcohort of SLAS-2 participants without CKD (eGFR > 60 mL/min/1.73 m2) at baseline (N = 786) who were followed up at 3-5 years. RESULTS: In baseline cross-sectional analyses adjusting for other risk factors, low, moderate, and high MR was significantly associated with decreasing eGFR coefficients of -1.5, -3.3, and -5.0 mL/min/1.73 m2 respectively, and increasing CKD odds ratios of 1.81, 2.18, and 3.11 respectively. In longitudinal analysis, low, moderate, and high MR was significantly associated with increased risk of eGFR (>25%) decline (odds ratio of 2.37, 3.34, and 2.18 respectively). CONCLUSIONS: Among older adults without advanced kidney disease, MR is associated with poor kidney function and increased risk of kidney function decline and CKD. Preventive interventions to modify MR may help to reduce the deterioration of renal function in older people.

Lifetime pathogen burden, inflammatory markers, and depression in community-dwelling older adults.

The link between pathogen exposure and mental health has long been hypothesized, but evidence remains limited. We investigated the association of seropositivity to common pathogens and total pathogen burden with depression and mental health and explored the role of mediating inflammatory cytokines. We profiled in 884 participants in the Singapore Longitudinal Ageing Studies, mean (SD) age: 67.9 (8.1) years, their seropositivities for 11 pathogens (CMV, HSV 1, HSV 2, HHV-6, EBV, VZV, RSV, Dengue, Chikungunya, H. Pylori and Plasmodium) and pathogen burden, Geriatric Depression Scale (GDS) score at baseline and 3-4 and 6-8 years follow-up, and baseline Mental Component Score (MCS) of 12-Item Short Form Survey (SF-12). Inflammatory markers included CRP, TNF-α, IL-6, MIP-1α, sgp130, sTNF-RI, sTNF-RII, C3a, and MCP-2. Controlling for age, sex, ethnicity, education, marital status, living alone, and smoking status, high pathogen burden (7 + cumulative infections) compared to low pathogen burden (1-5 cumulative infections) was significantly associated with period prevalence (the highest GDS score from baseline and follow-up measurements) of depressive symptoms (OR = 2.36, 95% CI = 1.05-5.33) and impaired mental health (OR = 2.25, 95% CI = 1.18-4.30). CMV seropositivity and HSV1 seropositivity, which are highly prevalent and most widely studied, were associated with estimated 2-fold increased odds of depression, but only HSV1 seropositivity was significantly associated with depression after adjusting for confounders. Notably, adjusted for confounders, RSV, H. pylori and Plasmodium seropositivity were significantly associated with increased odds, and Dengue seropositivity was associated with unexpectedly deceased odds of depressive symptoms and impaired mental health. The association of pathogen exposure with depression and mental health were at least in parts explained by inflammatory markers. Adding certain inflammatory markers to the models attenuated or weakened the association. Bootstrap method showed that MIP-1α significantly mediated the association between pathogen burden and mental health. In conclusion, lifelong pathogen burden and specific infections are associated with depression and impaired mental health in older adults.

Four New Triterpenoid Saponins from the Root of Ilex centrochinensis.

One new siaresinolic acid saponin (1) and three new rotundic acid saponins (2-4) were isolated from the roots of Ilex centrochinensis. Their structures were confirmed by detailed analysis of standard spectroscopic data (IR, MS, 1D and 2D NMR). Compounds 1-4 exhibited anti-inflammatory activity by inhibiting nitric oxide production in a lipopolysaccharide-induced RAW264.7 cell inflammatory model. However, they showed no significant lipid-lowering activity against the production of triglycerides in the lipid-accumulation model of HepG2 cells induced by oleic acid.

The LncRNA CASC11 Promotes Colorectal Cancer Cell Proliferation and Migration by Adsorbing miR-646 and miR-381-3p to Upregulate Their Target RAB11FIP2.

BACKGROUND: We previously reported that the long non-coding RNA (lncRNA) CASC11 promotes colorectal cancer (CRC) progression as an oncogene by binding to HNRNPK. However, it remains unknown whether CASC11 can act as a competitive endogenous RNA (ceRNA) in CRC. In this study, we focused on the role of CASC11 as a ceRNA in CRC by regulating miR-646 and miR-381-3p targeting of RAB11FIP2. METHODS: We identified the target microRNAs (miRNAs) of CASC11 and the target genes of miR-646 and miR-381-3p using bioinformatic methods. A dual-luciferase reporter assay was performed to validate the target relationship. Quantitative real-time PCR (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were used to measure the RNA and protein expression levels. Rescue experiments in vitro and in vivo were performed to investigate the influence of the CASC11/miR-646 and miR-381-3p/RAB11FIP2 axis on CRC progression. RESULTS: We found that CASC11 binds to miR-646 and miR-381-3p in the cytoplasm of CRC cells. Moreover, miR-646 and miR-381-3p inhibitors reversed the suppressive effect of CASC11 silencing on CRC growth and metastasis in vitro and in vivo. We further confirmed that RAB11FIP2 is a mutual target of miR-646 and miR-381-3p. The expression levels of CASC11 and RAB11FIP2 in CRC were positively correlated and reciprocally regulated. Further study showed that CASC11 played an important role in regulating PI3K/AKT pathway by miR-646 and miR-381-3p/RAB11FIP2 axis. CONCLUSION: Our study showed that CASC11 promotes the progression of CRC as a ceRNA by sponging miR-646 and miR-381-3p. Thus, CASC11 is a potential biomarker and a therapeutic target of CRC.

Pathogenic load and frailty in older adults: Singapore longitudinal ageing study.

Human evidence for the role of continuous antigenic stimulation from persistent latent infections in frailty is limited. We conducted a nested case-control study (99 deceased and 43 survivors) of participants aged 55 and above in a longitudinal ageing cohort followed up from 2003 to 2017. Using blood samples and baseline data collected in 2003-2004, we examined the association of pathogenic load (PL) count of seropositivity to 10 microbes (viruses, bacteria and mycoplasma) with cumulated deficit-frailty index (CD-FI) and the physical frailty (PF) phenotype, and mortality. Controlling for age, sex, education, smoking and alcohol histories, high PL (7-9) versus low PL (3-6) was associated with an estimated increase of 0.035 points in the CD-FI (Cohen's D=0.035 / 0.086, or 0.41). High PL was associated with 8.5 times odds of being physically frail (p=0.001), 2.8 times odds of being weak (p=0.010), 3.4 times odds of being slow (p=0.024), and mortality hazard ratio of 1.53 (p=0.046). There were no significant associations for specific pathogens, except marginal associations for Epstein-Barr virus and Chikungunya. Conclusion: A high pathogenic load of latent infections was associated with increased risks of frailty and mortality.

Associations of lifestyle activities and a heathy diet with frailty in old age: a community-based study in Singapore.

Frailty is an age-related state characterized by a reduced physiological reserve, and is associated with adverse health outcomes in the elderly. We analyzed the data from 895 adults aged 60 years and above, and investigated the relationships between midlife and late-life social activities, intellectual activities, working hours, and dietary habits and frailty status. Participation in social or intellectual activities in late life was less prevalent among those who were frail than among those who were robust. A greater proportion of those who were frail had worked long hours in midlife. After adjustment for confounders, participating in social activities or intellectual activities in late life was associated with a reduced risk for prefrailty and frailty, while working long hours in midlife was associated with a higher risk for frailty. The risk of frailty decreased with increasing healthy diet scores in midlife and late life. When the results were stratified by gender, late-life participation in social activities and midlife or late-life participation in intellectual activities correlated negatively with prefrailty/frailty only in women. Our study suggests that social and intellectual activities are inversely associated with frailty status, but the association seems to differ based on gender.

Neoadjuvant chemotherapy in combination with surgery in the treatment of local advanced breast cancer.

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy combined with surgery on locally advanced breast cancer and its prognosis. METHODS: One hundred and fifty-four patients with locally advanced breast cancer who were admitted to our hospital from February 2014 to April 2015 were selected as the study subjects. They were divided into an observation group and a control group according to the principle of random equalization, 77 each group. The observation group was treated with TAC scheme, neoadjuvant chemotherapy combined with modified radical resection, and continuously treated with the same scheme after operation until the end of the course of treatment. The control group was treated with modified radical resection and TAC scheme. The clinical efficacy of the two groups was observed, and the perioperative indications, prognosis and occurrence of adverse reactions were compared between the two groups. RESULTS: The total effective rate of the observation group was 76.62%, significantly higher than that of the control group (55.84%, P<0.05). The observation group had shorter operation time and hospitalization time and less bleeding amount compared to the control group (P<0.05). The metastasis rate and recurrence rate of the observation group were significantly lower than those of the control group (P<0.05); there was a significant difference between the two groups (P<0.05). The one-year and three-year survival rates of the observation group were significantly higher than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups after operation (P>0.05). CONCLUSION: Preoperative neoadjuvant chemotherapy in combination with TAC scheme can reduce the difficulty of operation, improve the curative effect of patients, significantly improve the prognosis of patients and prolong the survival time, which is worth clinical application.

IPO5 promotes the proliferation and tumourigenicity of colorectal cancer cells by mediating RASAL2 nuclear transportation.

BACKGROUND: Karyopherin nuclear transport receptors play important roles in tumour development and drug resistance and have been reported as potential biomarkers and therapeutic targets for tumour treatment. However, IPO5, one of the karyopherin nuclear transport receptor family members, remains largely uncharacterized in tumour progression. METHODS: The TCGA data, quantitative reverse transcription-PCR (qRT-PCR), western blotting, and IHC analyses were used to detect IPO5 expression in CRC tissues. A series of in vivo and in vitro experiments was utilized to demonstrate the function of IPO5 in CRC tissues. Mass spectrometry (MS), CO-IP technology, subcellular fractionation, and immunofluorescence were utilized to investigate the possible mechanisms of CRC. RESULTS: IPO5 was highly expressed and positively correlated with the clinicopathological characteristics of colorectal cancer tissues. Functional experiments indicated that IPO5 could promote the development of CRC. Mechanistically, we screened RASAL2, one cargo of IPO5, and further confirmed that IPO5 bound to the NLS sequence of RASAL2, mediating RASAL2 nuclear translocation and inducing RAS signal activation, thereby promoting the progression of CRC. CONCLUSIONS: Together, our results indicate that IPO5 is overexpressed in colorectal cancer cells. By transporting RASAL2, IPO5 may play a crucial role in CRC.

SSH3 facilitates colorectal cancer cell invasion and metastasis by affecting signaling cascades involving LIMK1/Rac1.

Slingshot phosphatase 3 (SSH3) is a member of the SSH phosphatase family that regulates actin filament dynamics. However, its role in cancer metastasis is relatively unclear compared to that of SSH1. Here, we showed that SSH3 was upregulated in colorectal cancer (CRC). Of note, SSH3 was upregulated in the tumor thrombus and lymph node metastasis compared with that in paired primary CRC tissues. High SSH3 expression was associated with the aggressive phenotype of CRC and may be an independent prognostic factor for the poor survival of patients with CRC. SSH3 significantly enhanced the invasion and metastasis of CRC cells in vitro and in vivo. Moreover, SSH3 regulated the remodeling of actin, which is involved in the cytoskeleton signaling pathway, through its interaction with LIMK1/Rac1 and subsequently promoted CRC cell invasion and metastasis. Our data elucidate an important role for SSH3 in the progression of CRC, and SSH3 may be considered a potential therapeutic target for CRC.

Identification of inflammatory and vascular markers associated with mild cognitive impairment.

Biochemical processes have been associated with the pathogenesis of mild cognitive impairment (MCI) and dementia, including chronic inflammation, dysregulation of membrane lipids and disruption of neurotransmitter pathways. However, research investigating biomarkers of these processes in MCI remained sparse and inconsistent. To collect fresh evidence, we evaluated the performance of several potential markers in a cohort of 57 MCI patients and 57 cognitively healthy controls. MCI patients showed obviously increased levels of plasma TNF-α (p = 0.045) and C-peptide (p = 0.004) as well as decreased levels of VEGF-A (p = 0.042) and PAI-1 (p = 0.019), compared with controls. In addition, our study detected significant correlations of plasma sTNFR-1 (MCI + Control: B = -6.529, p = 0.020; MCI: B = -9.865, p = 0.011) and sIL-2Rα (MCI + Control: B = -7.010, p = 0.007; MCI: B = -11.834, p = 0.003) levels with MoCA scores in the whole cohort and the MCI group. These findings corroborate the inflammatory and vascular hypothesis for dementia. Future studies are warranted to determine their potential as early biomarkers for cognitive deficits and explore the related mechanisms.

Hallmarks of improved immunological responses in the vaccination of more physically active elderly females.

Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions. Immunosenescence is primarily driven by chronic immune activation and physical activity interventions have demonstrated the potential to reduce the risk of complications in the elderly by modulating inflammation and augmenting the immune system. Since poor vaccination outcome is a hallmark of immunosenescence, the assessment of vaccine efficacy provides a window to study the immunological effects of regular physical activity. Using an accelerator-based study, we demonstrate in a Singaporean Chinese cohort that elderly women (n=56) who walk more after vaccination display greater post-vaccination expansion of monocytes and plasmablasts in peripheral blood. Active elderly female participants also demonstrated lower baseline levels of IP-10 and Eotaxin, and the upregulation of genes associated with monocyte/macrophage phagocytosis. We further describe postive correlations between the monocyte response and the post-vaccination H1N1 HAI titres of participants. Finally, active elderly women reveal a higher induction of antibodies against Flu B in their 18-month second vaccination follow-up. Altogether, our data are consistent with better immunological outcomes in those who are more physically active and highlight the pertinent contribution of monocyte activity.

IRF1 inhibits the proliferation and metastasis of colorectal cancer by suppressing the RAS-RAC1 pathway.

BACKGROUND: Interferon regulatory factor 1 (IRF1) plays a role in the immune response, cellular necrosis, DNA damage, and DNA repair, offering an attractive target for anticancer treatment. However, little is known about the role of IRF1 in the regulation of CRC progression. METHODS: Quantitative reverse transcription-PCR, Western blot, and immunohistochemistry were used to examine the expression level of IRF1; Cell Counting Kit-8, migration assay, and xenograft mouse models were used to examine the function of IRF1 in CRC cell lines; a ChIP assay was used to examine the binding between IRF1 and Ras association domain-containing protein 5 (RASSF5). RESULTS: IRF1 expression was lower in colorectal cancer (CRC) than in normal mucosa and the IRF1 expression level was inversely associated with CRC metastasis. In addition, IRF1 could inhibit CRC cell proliferation, migration, and metastasis in vivo and in vitro; IRF1 also induced cell cycle arrest but had no effect on cell apoptosis. IRF1 enhanced the expression of RASSF5 by increasing its promoter activity. Moreover, this study revealed a novel mechanism for inhibiting the RAS-RAC1 pathway by overexpression of RASSF5. CONCLUSION: Altogether, the results indicate that IRF1, which promotes RASSF5 expression, suppresses CRC metastasis and proliferation possibly through downregulation of the RAS-RAC1 pathway.

Biomarker Signatures Predicting 10-Year All-Cause and Disease-Specific Mortality.

Novel wide array blood biomarkers of multisystem dysregulation, compared to conventional clinical and blood biomarkers, are potentially able to provide more accurate prognostic information of long-term mortality risks. We identified biomarker signatures of all-cause and disease-specific mortality from a comprehensive range of analytes related to six major physiological functions: cytokine, chemokine, and growth factors; glucose metabolism regulators and adipokines; adhesion molecules; acute phase response; pathogen-specific antibodies; and bone remodeling. A total of 144 elderly were prospectively followed up on mortality for median 136 months. Plasma levels of 93 biomarkers measured by enzyme-linked immunosorbent assay, Luminex, FlowCytomix, DNA quantification, and recombinant DNA technology at baseline were compared among deceased and surviving elderly and in a referent group of 72 healthy young adults. The elderly, and especially deceased elderly, exhibited differential profiles of the composite index of each physiological function from young adults. In Cox regression, we identified and validated in an independent cohort of 357 elderly the specific and common biomarkers predicting all-cause, cardiovascular disease-related, neoplasm-related, and respiratory disease-related mortalities after controlling age, sex, and major comorbidities. These biomarkers had 74.3% correct classification for deceased elderly from surviving elderly. We reported for the first time, stem cell growth factor-ß and gastric inhibitory polypeptide as specific biomarkers of mortality risk.

MicroRNA-152 Acts as a Tumor Suppressor MicroRNA by Inhibiting Krüppel-Like Factor 5 in Human Cervical Cancer.

Aberrant expression of microRNA-152 (miR-152) is frequently observed in human cancers including ovarian cancer, breast cancer, prostate cancer, and gastric cancer. However, its expression and functional role in cervical cancer (CC) are poorly understood. Also, the association between miR-152 and Krüppel-like factor 5 (KLF5) expression in CC remains unclear. In this study, analyzing the expression of miR-152 by quantitative real-time PCR (qRT-PCR) revealed it was sharply reduced in CC tissues and cell lines. In addition, the negative correlation of miR-152 expression and KLF5 expression was observed. The dual-luciferase reporter assay validated that KLF5 was a target of miR-152. In vitro functional assays revealed that miR-152 could inhibit cell proliferation and cell cycle progression through regulating the expression of KLF5. Taken together, our study suggested that miR-152 functions as a tumor suppressor in CC, and the miR-152/KLF5 axis may provide novel therapeutic targets for CC treatment.