Effect of exercise-based cancer rehabilitation via telehealth: a systematic review and meta-analysis.

PURPOSE: Exercise-based cancer rehabilitation via digital technologies can provide a promising alternative to centre-based exercise training, but data for cancer patients and survivors are limited. We conducted a meta-analysis examining the effect of telehealth exercise-based cancer rehabilitation in cancer survivors on cardiorespiratory fitness, physical activity, muscle strength, health-related quality of life, and self-reported symptoms. METHODS: PubMed, Web of Science, and reference lists of articles related to the aim were searched up to March 2023. Randomized controlled clinical trials were included comparing the effect of telehealth exercise-based cancer rehabilitation with guideline-based usual care in adult cancer survivors. The primary result was cardiorespiratory fitness expressed by peak oxygen consumption. RESULTS: A total of 1510 participants were identified, and ten randomized controlled trials (n = 855) were included in the meta-analysis. The study sample was 85% female, and the mean age was 52.7 years. Meta-analysis indicated that telehealth exercise-based cancer rehabilitation significantly improved cardiorespiratory fitness (SMD = 0.34, 95% CI 0.20, 0.49, I2 = 42%, p < 0.001) and physical activity (SMD = 0.34, 95% CI, 0.17, 0.51, I2 = 71%, p < 0.001). It was uncertain whether telehealth exercise-based cancer rehabilitation, compared with guideline-based usual care, improved the quality of life (SMD = 0.23, 95%CI, -0.07, 0.52, I2 = 67%, p = 0.14) body mass index (MD = 0.46, 95% CI, -1.19, 2.12, I2 = 60%, p = 0.58) and muscle strength (SMD = 0.07, 95% CI, -0.14, 0.28, I2 = 37%, p = 0.51). CONCLUSION: This meta-analysis showed that telehealth exercise cancer rehabilitation could significantly increase cardiorespiratory fitness and physical activity levels and decrease fatigue. It is uncertain whether these interventions improve quality of life and muscle strength. High-quality and robust studies are needed to investigate specific home-based exercise regimens in different cancer subgroups to increase the certainty of the evidence.

Effectiveness of dance movement therapy and dance movement interventions on cancer patients' health-related outcomes: a systematic review and meta-analysis.

OBJECTIVES: This review examined the effectiveness of using dance movement therapy (DMT) and dance movement interventions (DMIs) with cancer and palliative care patients. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six databases were searched from inception to July 9, 2022, without limits on year or age. Searching was updated on July 10, 2023. The risk of bias was assessed by the Cochrane (RoB 2) and ROBINS-I tools. Meta-analyses were conducted to pool estimates of the effects of DMT and DMI on patients' health-related outcomes. A narrative synthesis of outcomes was performed where meta-analysis was not appropriate. RESULTS: Among a total of 16 studies included in this review, nine were randomized controlled trials and seven were non-randomized trials, with a total of 893 participants. Only six of these studies were fully or partially described as true DMTs (some with less clarity than others), whereas the majority (n = 10) were DMIs with unclear therapeutic alignment. Most studies focused on female patients with breast cancer. Cancer patients undergoing palliative care received little attention. The overall risk of bias from the evaluated studies was high. Meta-analysis of two trials revealed that DMTs had no effect on QOL in cancer patients (SMD - 0.09, 95% CI - 0.21-0.40, P = 0.54), while narrative analysis and non-randomized trials showed no overall effect of DMTs on anxiety, depression, body image, self-esteem, or sleep disturbance but significant positive effects on perceived stress, pain severity, and pain interference. DMIs had significant positive effects on cancer patients' depression (SMD - 0.53, 95% CI - 0.93 to - 0.14, P = 0.008) and fatigue (SMD - 0.42, 95% CI - 0.70 to - 0.14, P = 0.003). DMI trials synthesized narratively showed an effect on patients' body image, self-esteem, physical function, right and left handgrip strength, life satisfaction, and the mental component of QOL. CONCLUSION: Both DMT and DMIs had promising effects on several health outcomes, but results were inconsistent, and the evidence was weak. The reviewed studies' low evidence quality and small sample sizes affected the findings' robustness and reliability. Large-scale, high-quality randomized controlled trials with sufficient sample sizes, and clear and veracious DMT and DMI protocols and data are required to provide more credible research evidence and influence practice.

Technology-assisted cardiac rehabilitation for coronary heart disease patients with central obesity: a randomized controlled trial.

BACKGROUND: Limited empirical evidence is available regarding the effect of technology-assisted cardiac rehabilitation (TACR) among coronary heart disease (CHD) patients with central obesity. AIM: To determine the effects of 12-week TACR on health outcomes of patients with CHD. DESIGN: Two-arm randomized controlled trial. SETTING: Cardiovascular department of a regional hospital. POPULATION: Coronary heart disease patients with central obesity. METHODS: The study randomized 78 hospitalized CHD patients to receive either the 12-week TACR intervention or usual care. Guided by social cognitive theory, the intervention began with an in-person assessment and orientation session to assess and identify individual risks and familiarize with the e-platform/device before discharge. After discharge, patients were encouraged to visit the interactive CR website for knowledge and skills acquisition, data uploading, use the pedometer for daily step tracking, and interact with peers and professionals via social media for problem-solving and mutual support. Data were collected at baseline (T0), six-week (T1), and 12-week (T2). RESULTS: Participants in the intervention group showed significant improvement in daily steps at six weeks but not 12 weeks (T1: ß=2713.48, P=0.03; T2:ß=2450.70, P=0.08), weekly sitting minutes (T1: ß=-665.17, P=0.002; T2: ß=-722.29, P=0.02), and total (vigorous, moderate, and walking) exercise at 12-week (ß=-2445.99, P=0.008). Improvement in health-promoting lifestyle profile (T1: ß=24.9, P<0.001; T2: ß=15.50, P<0.001), smoking cessation (T2: ß=-2.28, P<0.04), self-efficacy (T2: ß=0.63, P=0.02), body mass index (T1:ß =-0.97, P=0.03; T2: ß=-0.73, P=0.04) and waist circumferences (T1: ß =-1.97, P=0.003; T2: ß =-3.14, P=0.002) were identified. CONCLUSIONS: Results indicated the effectiveness of the TACR intervention in improving healthy behaviors and anthropometric parameters for CHD patients with central obesity. Individual assessment, collaborative action planning, and ongoing obesity management support should be highlighted in TACR programs for CHD patients. CLINICAL REHABILITATION IMPACT: Central obesity should be assessed and highlighted in TACR intervention as an independent risk factor that requires corresponding behavior change and body fat management.

Systematic review and meta-analysis of the effectiveness of expressive writing disclosure on cancer and palliative care patients' health-related outcomes.

OBJECTIVES: This review aimed to synthesize the available evidence on the effectiveness of expressive writing (EW) on health outcomes of patients with cancer. METHODS: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six databases were searched from 1986 to 9 July 2022. The searches were updated on 3 October 2023. Methodological quality was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and ROBINS-I tool for non-RCTs Mixed Methods Appraisal Tool. Narrative synthesis of outcomes was performed where meta-analysis was not appropriate. RESULTS: Thirty-four studies with 4316 participants were identified, including 31 RCTs and three non-RCTs. Twenty-one studies focused on women with breast cancer; the remainder recruited people with various cancer types. There was a significant improvement in fatigue (SMD = - 0.3, 95% CI - 0.55 to - 0.66, P = .002), passive mood (MD = - 3.26, 95% CI = - 5.83 to - 0.69, P = 0.001), and the physical dimension of quality of life (MD = 3.21, 95% CI 0.18 to 6.25, P = 0.04) but not for anxiety, depression, and global quality of life among patients who participated in EW when compared with control groups. CONCLUSION: Findings showed some benefits of EW for people with cancer, but not necessarily in anxiety or depression. Heterogeneity in the delivery of interventions and their content, and shortcomings in the methodologies used highlight the need for stronger evidence in the field through high-quality trials and consistencies in the protocol, focusing on outcomes that this review highlighted as potential outcome targets.

Palliative Care for Older Adults Hospitalized for Stroke From the Informal Caregivers' Perspectives: A Qualitative Study.

BACKGROUND: International guidelines have promoted palliative care (PC) for stroke survivors, but definition and implementation have been less than ideal. This practice gap is more prominent in China, where discussion of death remains taboo. AIM: The aim of this study was to explore the perspectives of PC among caregivers of hospitalized patients with stroke. DESIGN AND SETTING: A descriptive qualitative study design was used. Seventeen in-depth interviews with bedside caregivers in a first-rank tertiary hospital (general hospital with bed capacity exceeding 500) in China were analyzed thematically. RESULTS: "Promoting comfort" stands at the core of PC and was operationalized by "meeting physical care needs," "ensuring communication," "providing psychoemotional care," "providing cognitive stimulation," and "avoiding discussion on death and dying." Caregivers who took care of older adults for a long time have described the use of "cognitive stimulation" to promote patients' positive emotional and cognitive reactions. All interviewees avoided mentioning "death" to protect patients' feelings, because they believed discussion of death was hurtful. CONCLUSIONS: The high care demand for patients with stroke is a defining feature of stroke PC and should be recognized in addition to its prognosis estimation to promote this concept. The healthcare system should integrate PC as part of the regular service for patients with severe stroke to shift the focus of care from survival to promotion of comfort. A discussion of the dying process requires sensitivity and should be approached in a discussion of advanced PC planning, which views death as a meaningful transition.

Home-based cardio-oncology rehabilitation using a telerehabilitation platform in hematological cancer survivors: a feasibility study.

PURPOSE: Cardiovascular disease is a competing mortality cause in hematological cancer survivors due to toxic oncological treatment, accumulation of risk factors, and decline of cardiorespiratory fitness. Cardio-oncology rehabilitation (CORE) is an emerging treatment model to optimize the prognosis of hematological cancer patients and survivors; however, its accessibility during the COVID-19 pandemic is poor. The study aimed to evaluate the feasibility, safety, and effect of a 12-week home-based CORE intervention in telerehabilitation approach among hematological cancer survivors. METHODS: A prospective single-arm interventional study was conducted at a faculty hospital in Brno, Czech Republic. This study provided 12 weeks of the home-based CORE using a telerehabilitation approach that allows remote supervision by a clinician from a medical facility. The telerehabilitation approach consists of three components: a heart rate sensor (PolarM430, Kempele, Finland), a web platform compatible with the sensor, and telesupervising via telephone call (1 call per week). To improve adherence, a physiotherapist called participants to assess or address adverse effects, exercise feedback, and participant-related concerns. The anthropometry, body composition, and cardiorespiratory fitness were measured immediately after the intervention. RESULTS: Eleven hematological cancer survivors with an average age of 60.3 ± 10 years participated in the study. Most participants were diagnosed with Follicular lymphoma and received maintenance treatment. Participants had a significant (p < 0.05) increase in cardiorespiratory fitness by 2.6 ml/kg/min; and in peak workload, from 143.3 ± 60.6 W to 158.6 ± 67.5 W (p < 0.05). Improvement in anthropometry and body composition was observed but yielded no statistical significance. Most (80%) participants completed the three times/per week telesupervising exercise session for 12 weeks.No adverse event was identified. CONCLUSION: Findings from this study suggest that home-based CORE may provide hematological cancer survivors with an increase in CRF during the rehabilitation period after hospital discharge. The telerehabilitation CORE model is effective, feasible, safe, and has demonstrated good adherence. Further randomized controlled efficacy study with larger sample size is needed before clinical implementation. CLINICAL TRIAL REGISTRATION: Clinical trial registration number NCT04822389 (30/03/2021).

Exploring the Relationship Between Usage and Outcomes of an eHealth Cardiac Rehabilitation Intervention: Subanalysis of a Randomized Controlled Trial.

This study aimed to explore the relationship between patients' characteristics and eHealth cardiac rehabilitation adherence and between eHealth usage metrics and behavior change. A subanalysis of 73 patients in the intervention group who received eHealth cardiac rehabilitation was conducted. Usage metrics on the number of Web site logins, health data uploads, and times of peer interaction and professional consultation were captured. Linear regression analysis was used. Participants (n = 73) were predominantly male with an average age of 55.53 (SD, 7.3) years. Younger age, having been treated with percutaneous coronary intervention, and hypertension predict higher Web site logins, whereas higher education, comorbidity with hypertension and diabetes, larger family size, and having been treated with percutaneous coronary intervention predict higher chatroom engagement. The Web site logins, Web site data uploads, chatroom nurse consultation, age, number of family members, drinking, and coresidency status were identified as significant correlates and explained 41.8% of the improvement in behavior change. This study demonstrated empirical evidence that Web site visits, health data uploads, and nurse consultations are crucial for behavior modification. Further studies may monitor usage metrics and investigate self-reported usage to explore the role of peer interaction in modifying behavior. Trial registration: Chinese Clinical Trial Registry: ChiCTR1800020411.

Psychological distress and associated factors among Palestinian advanced cancer patients: A cross-sectional study.

Objective: There is limited research exploring the experiences of people living with advanced cancer in the Gaza Strip (GS), Palestine. Thus, this study aimed to determine the level of psychological distress, anxiety, and depression among advanced cancer patients in the GS and identify factors associated with a high level of distress. Materials and methods: A secondary analysis was performed using primary data from a larger study focusing on supportive care needs in advanced cancer patients in GS. Three hundred sixty-one patients agreed to participate and filled out the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression was conducted to identify factors associated with high distress levels. Results: Over two-thirds of advanced cancer patients (70.6%) reported a high level of distress. They also reported a significantly higher distress level than patients with early cancer (96.5 vs. 3.5%; p = 0.001). About 92.8% of participants reported depression and anxiety symptoms. Physical, emotional, and practical problems were the primary sources of distress. Breast cancer patients were more likely to have psychological distress than colon and stomach cancer patients. Newly diagnosed patients had a higher level of anxiety, depression, and distress than those who had a cancer diagnosis for an extended period. Conclusion: Patients with advanced cancer in the GS exhibited a significantly higher level of psychological distress, depression and anxiety than patients with advanced cancer elsewhere. Efforts should be made to identify psychological distress as a routine part of oncology practice. Future research should further explore the causes of psychological distress in cancer patients in conflict zones and feasible mitigation strategies.

Policymakers' and patients' perspectives on breast cancer management in the Gaza Strip-Palestine: A qualitative study.

PURPOSE: This study aimed to explore the perspectives of policymakers and patients on breast cancer (BC) management in the Gaza Strip. METHODS: A descriptive qualitative study design was employed using semi-structured in-depth interviews with 13 policymakers and focus group discussions with 19 BC patients. The four criteria presented by Lincoln and Guba were used to evaluate the validity and reliability. Data were analysed using conventional content analysis approach. RESULTS: Three categories were generated from the qualitative data analysis: (1) limited human resources in the BC management, (2) inadequate institutional level service provision in the BC management, and (3) a lack of policy level support for the BC management. The current health services provided to Gazan BC patients are either fragmented or partially unavailable. The roles and responsibilities at the policy, system and individual levels were ambiguous. Policymakers attributed the fragmented BC services to the shortage of qualified healthcare professionals, inadequate training programmes for the staff, and lack of coordination among health institutions. Some patients expressed an insufficient knowledge about cancer screening tests, while others ignored screening for cultural reasons. CONCLUSION: Gaza's BC services are fragmented and not well-organised and they have received inadequate attention at the leadership and governance levels. The government in the Gaza Strip should strengthen its leadership to upgrade and develop the policies and strategies necessary for proper BC management, including an improved information system and cooperation with national and international institutions to secure funding for developing BC services and ensure medication availability.

[Effect of electroacupuncture on the expression of autophagy related protein in lung tissue of rats with chronic obstructive pulmonary disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Feishu" (BL13) on the expression of autophagy related proteins in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), so as to explore the mechanism of EA underlying improvement of COPD. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The COPD model was established by intratracheal infusion of Lipopolysaccharide (LPS, 1 mg/kg) and exposure in cigarette smoke. EA was applied to bilateral ST36 and BL13 for 30 min, once every other day for 2 weeks. The pulmonary function (forced vital capacity ï¼»FVCï¼½, forced expiratory volume in 0.1 s and 0.3 s ï¼»FEV0.1, FEV0.3ï¼½, FEV0.1/FVC and FEV0.3/FVC) was detected by animal pulmonary function analysis system. Histopathological changes of the airway and lung were displayed by H.E. staining. Autophagosomes in the airway and lung tissues were observed by electron microscope. The expression of AMP activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Unc-51 like autophagy activating kinase 1(ULK1), autophagy related protein ATG6(Beclin1)mRNAs in lung tissue were examined by quantitative real-time PCR. The expression of AMPK, mTOR, ULK1, Beclin1 and microtubule-associated protein 1 light chain 3 (LC3)proteins in lung tissue were examined by Western blot. The contents of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the broncho alveolar lavage fluid (BALF) were assayed by ELISA. RESULTS: Following modeling, the FVC, FEV0.1, FEV0.3, FEV0.1/FVC and FEV0.3/FVC levels were significantly decreased (P<0.01), the infiltration of inflammatory cells and the increase of autophagosomes were obvious in airway and lung tissue, the mRNA and protein expression of AMPK, ULK1, Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ were increased (P<0.01), while the mRNA and protein expression of mTOR were decreased (P<0.01), the contents of TNF-α and IL-6 in the BALF were increased in the model group compared with the normal group (P<0.01). After EA intervention, all the indexes mentioned above were completely reversed in the EA group relevant to the model group (P<0.01, P<0.05). CONCLUSION: EA at ST36 and BL13 can improve the lung function of COPD rats, which may be related to its effects in inhibiting the autophagy level and reducing the inflammation response in the lung.

Transplantation of a Novel Recombinant Adeno-Associated Virus (pAAV-HE1B19K-TE1A) Demonstrates Higher Anti-Tumor Effects in Tumor Cells.

BACKGROUND Oncolytic viruses (OVs) can specifically infect and kill tumor cells. Adeno-associated virus (AAV) is a widely-studied OV. This study aimed to construct a tumor-targeted recombinant AAV using genetic engineering technology. MATERIAL AND METHODS The transgene plasmid pAAV-HE1B19K-TE1A was constructed with 4 genes (hTERT, E1A, HKII, and E1B19K) and co-transfected with pAAV-RC and pHelper to tumor cells (HepG2, A549, BGC-803) and normal cells (HUVEC). rAAV was verified with fluorescence microscopy. Quantitative PCR (qPCR) assay was used to test the titer of rAAV in each cell line. Apoptosis was analyzed using qPCR and Western blot assay. MTT was used to detect the effect of rAAV on cell viability. RESULTS The pAAV-HE1B19K-TE1A transgene plasmid was successfully structured. pAAV-HE1B19K-TE1A was highly expressed in all tumor cells. The titers of pAAV-HE1B19K-TE1A in HepG2, A549, and BGC-803 were 7.4×107, 1.4×108, and 1.1×108 gc/µl, respectively. pAAV-HE1B19K-TE1A significantly decreased cell viability of tumor cells compared to that in HUVEC (p<0.05). pAAV-HE1B19K-TE1A remarkably triggered cleaved caspase 3 (C-caspase 3) activity in tumor cells compared to that in untransfected tumor cells (p<0.05). pAAV-HE1B19K-TE1A significantly induced release of cytochrome C (Cyto C) in tumor cells compared to that in untransfected tumor cells (p<0.05). pAAV-HE1B19K-TE1A demonstrated no toxicity to vital tissues of animals. CONCLUSIONS Tumor-targeted rAAV was successfully produced using the Helper-free system with recombinant plasmid, demonstrating high efficacy in decreasing viability of tumor cells without adverse effects on normal cells.

[Mechanism of gambogenic acid in resisting angiogenesis of lung cancer in vitro].

The aim of this paper was to observe the effect of gambogenic acid on angiogenesis of lung cancer and its preliminary mechanism. After culturing lung adenocarcinoma A549 cells, the conditioned medium was treated with gambogenic acid and then used to culture human umbilical vein endothelial cells (HUVECs) to establish the indirect contact cell co-culture system. A two-dimensional culture model of HUVEC was established with matrigel to observe the effect of gambogenic acid on angiogenesis. DAPI staining was used to observe the morphological changes in HUVEC cells after treatment with gambogenic acid under the fluorescence microscope. Annexin V-FITC/PI staining and flow cytometry analysis were used to determine gambogenic acid's effect on HUVEC cell apoptosis rate. The protein expressions of PI3K, p-PI3K, Akt, p-Akt were measured by Western blot. PTEN-siRNA was transfected into cells, and RT-PCR was used to detect the expression levels of PI3K and Akt genes. Gambogenic acid can significantly inhibit angiogenesis, and its inhibitory effect was dose-dependent. DAPI staining showed apoptotic morphological features of HUVEC cells under fluorescence microscope. Annexin V-FITC/PI staining showed that gambogenic acid induced apoptosis in HUVECs. The results of Western blot showed that the expressions of p-PI3K and p-Akt protein were down-regulated with gambogenic acid, while the expressions of PI3K and Akt protein was insignificant. The results of RT-PCR indicated that the expressions of PI3K and Akt protein were up-regulated by PTEN siRNA. Gambogenic acid can inhibit angiogenesis in lung cancer in vitro, and the mechanism of inhibiting angiogenesis may be related to the PI3K/Akt signaling pathway.

Cloning, expression, and characterization of three ribosomal protein S13 genes in Sophora flavescens / Clonagem, expressão e caracterização de três proteínas ribossômicas S13 genes em Sophora flavescens

To characterize the structure and function of ribosomal protein S13 (RPS13), we identified fulllength open reading frames (ORFs) of three RPS13 genes (RPS13-1, RPS13-2, and RPS13-3) of the Chinese medicinal plant, Sophora flavescens. The target genes were amplified by reverse transcription-olymerase chain reaction (RT-PCR), ligated into the pET22b(+) vector, and then transformed into Escherichia coli BL21 competent cells for protein expression. The physicochemical properties, protein motif, evolution, and structural organization of the three RPS13 genes were analyzed using bioinformatics tools. The full-length ORFs (453 bp) of the three RPS13 genes of S. flavescens were cloned, and each encodes a protein of 151 amino acids in length, and their expression was detected by Western blotting. Bioinformatics analysis showed that RPS13s are stable proteins that are closely related to the 40S RPS13s of Vigna radiate var. radiate. Their three-dimensional structures included three -helices at the C-terminal and four -helices at the N-terminal, and the two clusters of helices were connected by a long random coil, which may help maintain the dynamic bridging interactions between the large and small subunits of the ribosome. The full-length ORFs of three RPS13 genes of S. flavescens were successfully cloned and expressed in vitro. The study of the physicochemical properties, evolution, and secondary and three-dimensional structures of the three proteins will provide the theoretical basis for further studies on the function of RPS13s in plants.

Objetivo: Para caracterizar a estrutura e a função da proteína ribossomal S13 (RPS13), identificamos fases de leitura abertas (ORFs) completas de três genes RPS13 (RPS13-1, RPS13-2 e RPS13-3) da planta medicinal chinesa, Sophora flavescens. Métodos: Os genes alvo foram amplificados por reação em cadeia da polimerase por transcrição reversa (RT-PCR), ligados ao vetor pET22b(+), e então transformados em células competentes de Escherichia coli BL21 para expressão protéica. As propriedades físico-químicas, o motivo protéico, a evolução e a organização estrutural dos três genes RPS13 foram analisados utilizando ferramentas de bioinformática. Resultados: ORFs completos (453 pb) dos três genes RPS13 de S. flavescens foram clonados, e cada um codifica uma proteína de 151 aminoácidos de comprimento, e sua expressão foi detectada por western blotting. A análise de bioinformática mostrou que as RPS13s são proteínas estáveis que estão intimamente relacionadas com as 40S RPS13s de Vigna radiata var. radiate. Suas estruturas tridimensionais incluíam três -hélices no C-terminal e quatro -hélices no N-terminal, e os dois aglomerados de hélices eram conectados por uma longa bobina aleatória, o que pode ajudar a manter as interações de ponte dinâmicas entre o subunidades grandes e pequenas do ribossomo. Conclusões: As ORFs completas de três genes RPS13 de S. flavescens foram clonadas e expressas com sucesso in vitro. O estudo das propriedades físico-químicas, evolução e estruturas secundárias e tridimensionais das três proteínas fornecerão a base teórica para estudos adicionais sobre a função das RPS13s em plantas.

[Study of gambogenic acid-induced apoptosis of melanoma B16 cells through PI3K/Akt/mTOR signaling pathways].

OBJECTIVE: To discuss the mechanism of gambogenic acid (GNA) in inducing the apoptosis of melanoma B16 cells. METHOD: The inhibitory effect of GNA on the proliferation of B16 cells was measured by the methyl thiazolyl tetrazolium (MTT) assay. The effect of GNA on B16 cells was detected by the Hoechst 33258 staining. The transmission electron microscopy was used to observe the ultra-structure changes of B16 cells. The changes in PI3K, p-PI3K, Akt, p-Akt, p-mTOR, PTEN proteins were detected by the Western blotting to discuss the molecular mechanism of GNA in inducing the apoptosis of B16 cells. RESULT: GNA showed a significant inhibitory effect in the growth and proliferation of melanoma B16 cells. The cell viability remarkably decreased with the increase of GNA concentration and the extension of the action time. The results of the Hoechst 33258 staining showed that cells processed with GNA demonstrated apparent apoptotic characteristics. Under the transmission electron microscope, B16 cells, after being treated with GNA, showed obvious morphological changes of apoptosis. The Western blot showed a time-dependent reduction in the p-PI3K and p-Akt protein expressions, with no change in p-PI3K and p-Akt protein expression quantities. The p-mTOR protein expression decreased with the extension of time, where as the PTEN protein expression showed a time-dependent increase. CONCLUSION: GNA could inhibit the proliferation of melanoma B16 cells and induce their apoptosis within certain time and concentration ranges. Its mechanism in inducing the cell apoptosis may be related to PI3K/Akt/mTOR signaling pathways.

Acid-sensing ion channels activation and hypoxia upregulate Homer1a expression.

BACKGROUND: Recent studies have indicated that dynamic alterations in the structure of postsynaptic density (PSD) are involved in the pathogenesis of many central nervous system disorders, including ischemic stroke. Homer is the newly identified scaffolding protein located at PSD and regulates synaptic function. Homer1a, an immediate early gene, has been shown to be induced by several stimulations, such as glutamate, brain-derived neurotrophic factor, and trauma. However, whether acidosis mediated by acid-sensing ion channels (ASICs) and hypoxia during cerebral ischemia can change Homer1a expression remains to be determined. RESULTS: We investigated that acidosis and hypoxia selectively and rapidly upregulated Homer1a expression, but not Homer1b/c in cultured cortical neurons. We also found that Homer1a exhibited induction expression in brain cortex of the middle cerebral artery occlusion (MCAO) rats. Additionally, acid-evoked Homer1a mRNA induction depended on extracellular signal-regulated kinase1/2 (ERK1/2) and Akt activity, and ASIC1a-mediated calcium influx whereas hypoxia depended only on ERK1/2 activity. Also, we demonstrated that continuous acidosis and hypoxia resulted in pronounced cell injury and Homer1a knockdown with small interfering RNA aggravated this damage induced by 3 h acid and hypoxia incubation in neuro-2a cells. CONCLUSION: Homer1a might act as an activity-dependent regulator responding to extracellular stimuli during cerebral ischemia.

Fomentarols A-D, sterols from the polypore macrofungus Fomes fomentarius.

Four (1-4) hitherto unknown and seven (5-11) known ergostane-type sterols were isolated from the EtOH extract of the dried fruiting bodies of the polypore macrofungus Fomes fomentarius. On the basis of spectroscopic analysis, the structures of polyhydroxylated sterols 1-4 were elucidated to be (22E,24R)-3ß,5α,6ß,14α-tetrahydroxyergosta-7,9(11),22-triene (fomentarol A, 1), (22E,24R)-3ß,5ß,6α,7α-tetrahydroxy-8α,9α-dihydroergosta-14,22-diene (fomentarol B, 2), (22E,24R)-3ß,5α-dihydroxy-6ß-ethoxyergosta-7,22-diene (fomentarol C, 3), and (22E,24S)-3ß,25-dihydroxy-15α-O-ß-D-glucopyranosylergosta-7,22-dien-6-one (fomentarol D, 4), respectively. Rings A/B and B/C are in turn cis-fused in compound 2, which is uncommon in natural ergostane-type sterols. The potential biogenetic relationship of 2 and other ergostane-type sterols isolated from F. fomentarius was briefly discussed. Moderate cytotoxic effects of the isolated sterols against a small panel of human cancer cell lines were also established.

Glutathione prevents free fatty acids-induced oxidative stress and apoptosis in human brain vascular endothelial cells through Akt pathway.

AIMS: The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway. METHODS: After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP). We investigated whether the Akt pathway was involved in FFAs-induced signaling pathway alteration and whether GSH influenced the above effects. RESULTS: After being cultured in 200 µM FFAs for 72 h, the HBVECs proliferation significantly decreased; HBVECs apoptosis increased; the ROS levels increased; and the HBVECs MMP subsequently decreased. FFAs induced a significant decrease in phosphorylated active Akt. These alterations were obviously prevented when 1 mM GSH was added to culture medium containing FFAs, and the above effects of GSH were blocked by Akt inhibitor. CONCLUSION: GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway.

(24S)-ergostane-3ß,5α,6ß-triol from Hedyotis chrysotricha with inhibitory activity on migration of SK-HEP-1 human hepatocarcinoma cells.

The methanol extract of the whole plant of Hedyotis chrysotricha demonstrated cytotoxicity against SK-HEP-1 human hepatocarcinoma cells in a primary screening for novel antitumour agents. Bioassay-guided fractionation and purification led to an active principle (24S)-ergostane-3ß,5α,6ß-triol (1) along with four inactive compounds (2-5). The in vitro transwell migration assay showed that compound 1 remarkably reduced the migration of SK-HEP-1 cells by 78.9% at a dose of 30 µM, without any apoptotic effect on this cell line. Moreover, all the isolated compounds were further evaluated for their cytotoxicities against another four human cancer cell lines (MCF-7, NUGC3, SH-SY5Y and PC-3).

[Effect and mechanism of polyphyllin I on human cervical cancer cell HeLa in vitro].

OBJECTIVE: To study the effect and mechanism of polyphyllin I on human cervical cancer cell HeLa. METHODS: The cell growth and proliferation effect of Polyphyllin I on HeLa cells were measured by MTT assay; Hoechst 33258 fluorescent staining was used to record changes in cell morphology and morphological changes in mitochondria of Polyphyllin I before and after treatment on He La cells. Annexin V-FITC/PI staining was used to detect the ratio of tumor cell apoptosis by flow cytometry. Release of intracellular re active oxygen species (ROS) generation level in HeLa cells was determined by flow cytometry,Caspase-3 activity was measured by fluorescent assay kits. RESULTS: MTT results showed that Polyphyllin I could significantly suppressed the proliferation of HeLa cells and in time-and concentration-dependence manner. The intracellular ROS levels were increased dramatically and the mitochondrial membrane was decreased consistently. Caspase-3 proteins expression levels were increased after Polyphyllin I treatment. CONCLUSION: Polyphyllin I could inhibit HeLa cells growth and proliferation and its mechanism may be related to inducing cell apoptosis.

Gambogenic acid inhibits proliferation of A549 cells through apoptosis inducing through up-regulation of the p38 MAPK cascade.

Gamboge is a dry resin secreted from Garcinia hanburryi, and gambogenic acid (GNA) is one of the main active compounds of gamboge. We have previously demonstrated the anticancer activity of GNA in A549 cells and pointed out its potential effects in anticancer therapies. Previous studies reported that GNA induced apoptosis in many cancer cell lines and inhibited A549 tumor growth in xenograft of nude mice in vivo. However, the anticancer mechanism of GNA has still not been well studied. In this paper, we have investigated whether GNA-induced apoptosis is critically mediated by the p38 mitogen-activated protein kinase (MAPK) pathway. Our findings revealed that GNA could induce apoptosis, inhibit proliferation, down-regulate the expression of p38 and MAPK, increase the activations of caspase-9, caspase-3, and cytochrome c release. Furthermore, using SB203580, an adenosine triphosphate-competitive inhibitor of p38 MAPK, inhibit the expression of p-p38 and the experimental results show that it may promote the occurrence of apoptosis induced by GNA. Taken together, these results suggested that up-regulation of the p38 MAPK cascade may account for the activation of GNA-induced apoptosis.