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1.
Complement Ther Med ; 63: 102782, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34710559

RESUMO

BACKGROUND: Coprescription is a potential medical problem for older adults that could induce polypharmacy and subsequent complications. In Taiwan, Chinese herbal medicine (CHM) is popular among the older adults. Investigating the coprescription trends in Western medicine, CHM and dental medicine is important to avoid possible polypharmacy. METHODS: We analyzed data from the Longitudinal Health Insurance Database 2000 (LHID 2000) in Taiwan. Patients ≥ 60 years old who received coprescription of Western medicine, CHM and drugs for dental care from 1997 to 2013 were included. The odds ratio (OR) and 95% confidence interval (95% CI) were estimated by a logistic regression model for evaluating the correlation between baseline characteristics and coprescription. RESULTS: A total of 266,034 patients were included for the analysis. Most patients receiving coprescriptions lived in the northern Taiwan and with a monthly income lower than 20,000 new Taiwan dollars. The trends in older adults using Western medicine alone or CHM alone decreased over time, but the cohort using dental medicine alone had the opposite result. Decreased trends in coprescription with age were noted. The trends in the proportion of coprescription and the number of days of coprescription increased with the calendar year. Increased trends in the proportion of patients with coprescription were also found, except for the cohort of patients who used both Western medicine and CHM. Patients who were female, and aged 70-79 years were prone to receive coprescription. CONCLUSIONS: Coprescription in older patients is not uncommon in Taiwan. Healthcare providers and policymakers should be aware of the complex coprescription pattern in the older adults.

2.
J Clin Med ; 10(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34682857

RESUMO

Primary dysmenorrhea (PDM) is the most commonly encountered gynecological problem in reproductive-age women. Acupuncture has been suggested as an effective treatment of PDM that may modulate descending pain modulation systems. In the present study, we used resting-state functional magnetic resonance imaging to investigate possible changes in descending pain modulation systems after acupuncture treatment in women with PDM. Thirty-four right-handed adult women with PDM participated in this randomized, single-blinded, sham-controlled study. Each patient was randomly allocated to an 8-week verum or sham acupuncture intervention on the bilateral Sanyinjiao (SP6). Resting-state functional magnetic resonance imaging was conducted before, during, and after the intervention to measure the spontaneous activity in brain. After the 8-week intervention, both verum and sham groups reported decreased menstrual pain. However, the cessation of decreased functional connectivity (FC) between periaqueductal gray matter and the regions associated with affective pain modulation and attention-related pain modulation were found in the verum but not in the sham group after the 8-week intervention. More decreased FC has been found in the region associated with non-specific effects of acupuncture intervention after the early stage of acupuncture intervention. These results indicated that verum acupuncture may intercept the altered FC in descending pain modulation systems in PDM.

3.
Macromol Biosci ; 21(4): e2000382, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33522144

RESUMO

Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N6 -methyladenosine (m6 A) modifications during viral infection. Among of them, methyltransferase like-14 enzyme (METTL14) plays an important role in m6 A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal-protein nanoparticles designated GSTP1-MT3(Fe2+ ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon-beta (IFN-ß) production in vesicular stomatitis virus (VSV)-infected macrophages. Further investigation elucidates that a high dose of IFN-ß can promote the expression of METTL14, which has a well anti-VSV capacity. Moreover, it is found that other negative-sense single-stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative-sense single-stranded RNA viruses infections.

4.
J Sex Med ; 18(3): 487-492, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33504467

RESUMO

BACKGROUND: Vaginal flatus is involuntarily passing gas from the vagina. Women seldom voluntarily report it, and related data are limited. AIM: To investigate the prevalence of vaginal flatus in women with pelvic floor disorders and its impact on sexual function. METHODS: This was an observational study involving women who visited a urogynecologic clinic in a tertiary medical center. Patients were asked about their experience of vaginal flatus. Other evaluations included urodynamics, genital prolapse stage, and quality-of-life questionnaires, including the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. OUTCOMES: Clinical characteristics, vaginal anatomic landmarks, stage of prolapse, urodynamic parameters, and quality-of-life scores were compared between women with and without vaginal flatus. RESULTS: Among 341 women, 118 (35%) reported vaginal flatus, which was more common in those who were younger (a mean age of 49.3 ± 9.2 years; range 25-74 years vs 49.3 ± 9.2 years; range 25-74 years, P < .001) and sexually active (98% vs 55%, P < .001). Women with vaginal flatus had significantly worse sexual function (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, 16.3 ± 15.9 vs 30.9 ± 8.0, P < .001) and incontinence-related quality of life (Urogenital Distress Inventory, 23.4 ± 10.5 vs 17.8 ± 8.9, P = .039; Incontinence Impact Questionnaire, 25.5 ± 14.5 vs 17.2 ± 12.5, P = .012). For frequency and bother, 48 of 116 (46%) women reported often or always having symptoms during sexual activity, 5 of 34 (15%) when performing daily activities, and 4 of 31 (12%) when exercising, and 70 of 116 (60%) felt least moderate bothersome during sexual activity compared with 2 of 34 (5%) when performing daily activities and 6 of 31 (18%) when exercising. CLINICAL IMPLICATIONS: Vaginal flatus is prevalent in women with pelvic floor disorders, particularly in those who are younger and sexually active. STRENGTHS & LIMITATIONS: The strength of this study is to evaluate the sexual function with validated questionnaires. The lack of data after pelvic floor management is the major limitation. CONCLUSIONS: Among women with pelvic floor disorders, those with vaginal flatus reported poorer sexual function. Routine counseling should be considered for these patients. Lau H-H, Su T-H, Chen Y-Y, et al. The Prevalence of Vaginal Flatus in Women With Pelvic Floor Disorders and Its Impact on Sexual Function. J Sex Med 2021;18:487-492.


Assuntos
Distúrbios do Assoalho Pélvico , Prolapso de Órgão Pélvico , Adulto , Idoso , Feminino , Flatulência , Humanos , Pessoa de Meia-Idade , Distúrbios do Assoalho Pélvico/complicações , Distúrbios do Assoalho Pélvico/epidemiologia , Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/epidemiologia , Prevalência , Qualidade de Vida , Inquéritos e Questionários
5.
Int Urogynecol J ; 32(1): 17-25, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32564121

RESUMO

INTRODUCTION AND HYPOTHESIS: Recurrent urinary tract infections (rUTIs) are commonly encountered in postmenopausal women. Optimal non-antimicrobial prophylaxis for rUTIs is an important health issue. The aim of this study was to evaluate the use of estrogen in the prevention of rUTIs versus placebo. METHODS: Eligible studies published up to December 2019 were retrieved through searches of MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. We included randomized controlled trials of estrogen therapies versus placebo regarding the outcomes of preventing rUTIs. Changes in vaginal pH and estrogen-associated adverse events were also analyzed. RESULTS: Eight studies including 4702 patients (2367 who received estrogen and 2335 who received placebo) were identified. Five studies including 1936 patients evaluated the use of vaginal estrogen, which resulted in a significant reduction in rUTIs (relative risk, 0.42; 95% CI, 0.30-0.59). Three studies including 2766 patients evaluated the outcomes of oral estrogen in the prevention of UTIs and showed no significant difference in the number of rUTIs compared to treatment with placebo (relative risk, 1.11; 95% CI, 0.92-1.35). Two studies reviewed changes in vaginal pH and showed a lower pH (mean difference, -1.81; 95% CI, -3.10--0.52) after vaginal estrogen therapy. Adverse events associated with vaginal estrogen were reported, including vaginal discomfort, irritation, burning, and itching. There was no significance increase in the vaginal estrogen group (relative risk, 3.06; 95% CI, 0.79-11.90). CONCLUSIONS: Compared with placebo, vaginal estrogen treatment could reduce the number of rUTIs and lower the vaginal pH in postmenopausal women.


Assuntos
Pós-Menopausa , Infecções Urinárias , Estrogênios , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Urinárias/prevenção & controle
6.
Taiwan J Obstet Gynecol ; 59(4): 508-513, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32653121

RESUMO

OBJECTIVE: To investigate the outcomes of ultrasound-indicated cerclage in dichorionic-diamniotic (DCDA) twin pregnancies with a short cervical length. MATERIALS AND METHODS: This was a retrospective cohort study of DCDA twin pregnancies with a short cervical length (≤25 mm) from January 2000 to July 2017 to compare maternal and neonatal outcomes. Additional sub-analysis was performed by dividing the patients into two subgroups by a cervical length ≤15 mm and between 16 and 25 mm. RESULTS: One hundred and eight women were initially diagnosed with twin pregnancies and cervical insufficiency. After excluding cases not meeting the study criteria, 46 women were recruited for analysis, of whom 33 underwent ultrasound-indicated cerclage. The delivery age of the cerclage group was significantly later than the non-cerclage group (34.85 ± 3.91 versus 31.08 ± 5.25 weeks, p = 0.011), and the latency was significantly longer in the cerclage group than in the non-cerclage group (86.09 ± 41.32 versus 52.31 ± 33.24 days, p = 0.014). Sub-analysis revealed that these benefits were significant in the subgroup of a cervical length ≤15 mm. Both first twin (twin A) and second twin (twin B) had a significantly decreased rate of neonatal intensive care unit admission in the cerclage group. However, twin A had more promising outcomes with significantly decreased rates of neonatal respiratory distress syndrome (6.7% versus 50.0%, p = 0.004) and sepsis (0% versus 25.0%, p = 0.019). CONCLUSION: Ultrasound-indicated cerclage in DCDA twin pregnancies can decrease preterm birth and prolong the latency. It also decreases neonatal morbidity, and is especially beneficial for twin A.


Assuntos
Cerclagem Cervical , Medida do Comprimento Cervical , Nascimento Prematuro/prevenção & controle , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos , Estudos Retrospectivos , Taiwan
7.
Front Psychol ; 11: 1052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528385

RESUMO

Previous research has not clearly studied how the effects of emotional job demands on absenteeism likelihood are moderated by the contingent absenteeism-related regulatory institutional environments of low-income countries. In this regard, we surveyed 487 healthcare workers in a low-income country in order to test for the effect of emotional job demands on healthcare workers' absenteeism likelihood. We also explored the mediating role of work engagement and the contingent role of context-specific regulatory institutional environments on the link between emotional job demands and absenteeism likelihood. The main findings of this study are as follows: (1) emotional job demands have a direct positive effect on healthcare workers' absenteeism likelihood, (2) work engagement plays a mediating role on the link between emotional job demands and healthcare workers' absenteeism likelihood, and (3) the regulatory institutional environment related to absenteeism moderates the negative link between work engagement and absenteeism likelihood. Results in this study demonstrate the crucial role that the context-specific regulatory institutional environment related to absenteeism plays in suppressing the effect of emotional job demands on absenteeism likelihood when considered through the work-engagement pathway. The study's findings clarify the mechanism through which emotional job demands affect absenteeism likelihood in a low-income country context. The study thus offers a new refined theoretical perspective on how emotional job demands, work engagement, and context-specific regulatory institutional environments interact in ways that predict absenteeism likelihood.

8.
Life Sci ; 253: 117750, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32380078

RESUMO

AIM: Osteoarthritis (OA) is the main cause of disability and joint replacement surgery in the elderly. As a crucial cell survival mechanism, autophagy has been reported to decrease in OA. PHF23 is a new autophagy inhibitor which was first reported by us previously. This study aimed to explore the anti-autophagic mechanism of PHF23 to make it a possible therapeutic target of OA. MAIN METHOD: Lentiviral vectors specific to PHF23 were used on chondrocytes (C28/I2) to establish PHF23 overexpressed or knockdown stable cell strains. Interleukin (IL)-1ß (10 ng/mL) and chloroquine (CQ, 25 uM) were used as an inducer of OA and inhibitor of lysosome, respectively. Autophagy was evaluated by autophagosome formation using transmission electron microscopy (TEM) and western blot analysis of P62 and LC3B on different groups of cells. Effects of PHF23 on OA were evaluated by collagen II immunofluorescent staining and western blot analysis of OA-associated proteins MMP13 and ADAMTS5. Effects of PHF23 on AMPK and mTOR/S6K pathways and mitophagy were determined by western blot analysis. KEY FINDINGS: Knockdown of PHF23 enhanced IL-1ß-induced autophagy, while overexpression of PHF23 exerted the opposite effect. Knockdown of PHF23 protected chondrocytes against IL-1ß-induced OA by decreasing the levels of OA-associated proteins and increasing expression of Collagen II. Knockdown of PHF23 also increased mitophagy level and altered the phosphorylation levels of AMPK, mTOR, and S6K. SIGNIFICANCE: PHF23 downregulates autophagy, mitophagy in IL-1ß-induced OA-like chondrocytes and alters the activities of AMPK and mTOR/S6K, which suggests that PHF23 may be a possible therapeutic target for OA.


Assuntos
Autofagia/genética , Condrócitos/patologia , Proteínas de Homeodomínio/genética , Osteoartrite/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Sobrevivência Celular/genética , Células Cultivadas , Colágeno Tipo II/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/administração & dosagem , Lisossomos/metabolismo , Osteoartrite/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Serina-Treonina Quinases TOR/metabolismo
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1497-1503, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607304

RESUMO

OBJECTIVE: To investigate the effect of baicalin derivative 02-036 on proliferation and apoptosis human Burkitt lymphoma cell line CA46 and its related mechanisms. METHODS: The MTT assay and cell colony formation assay were used to measure the growth inhibition of CA46 cells after 02-036 treatment. The flow cytometry with AnnexinV-FITC/PI double staining was employed to detect the apoptosis induction effect of 02-036 on CA46 cells. Cell cycle distribution of CA46 cells was estimeted by using DNA ploid analysis. Western blot was used to determine the changes of apoptosis-related proteins, including C-MYC, BCL-2, Procaspase-9, Procaspase-3, PARP and Cleaved-PARP. RESULTS: Baicalin derivative 02-036 obviously inhibited the proliferation of CA46 cells, with dose- and time-dependent manner (r=0.963, r=0.992). The averaged IC50 value of CA46 cells was (6.04±0.11) µmol/L after 48-hour treatment. Low concentration of 02-036 could significantly inhibit the colony formation of CA46 cells. Flow cytometry analysis confirmed that 02-036 could effectively induce CA46 cell apoptosis. The apoptosis rate correlated with drug concentrations (r=0.959). Also, DNA ploid analysis showed that the cell cycle of CA46 was arrested in the S phase. The expression levels of BCL-2, Pro-caspase-9, Pro-caspase-3, PARP and C-MYC proteins decreased with a 02-036-dose dependent manner (r values were -0.990, -0.939, -0.971 and -0.967, respectively). In contrast, the expression level of cleaved-PARP increased with the same manner (r=0.920). CONCLUSION: Baicalin derivative 02-036 can effectively inhibit the proliferation and induce apoptosis of CA46 cells, and its related mechanisms may be correlated with the down-regulation of apoptosis-related molecule expression levels, such as BCL-2, Pro-caspase-9, Pro-caspase-3, PARP and C-MYC.


Assuntos
Linfoma de Burkitt , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Flavonoides , Humanos
10.
Int J Gynaecol Obstet ; 147(3): 382-388, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529463

RESUMO

OBJECTIVE: To evaluate risk factors associated with neonatal morbidity and mortality in pregnant women with preterm prelabor rupture of membranes (PPROM) after cervical cerclage. METHODS: A retrospective cohort study of singleton pregnancies with cervical insufficiency was conducted at a tertiary referral center in Taiwan from May 1, 2000 to July 31, 2017. Patients with PPROM after cerclage and delivered between 20 0/7 days and 36 6/7 days were recruited. Logistic and linear regression analyses were performed to evaluate various risk factors. RESULTS: Overall, 109 women were included. Mothers with a higher white blood cell count, a higher C-reactive protein (CRP) level, a lower amniotic fluid index, and chorioamnionitis were significantly associated with neonatal morbidity. Neonatal mortality was related to oligohydramnios (adjusted odds ratio [aOR] 2.98, 95% confidence interval [CI] 1.11-8.01) and chorioamnionitis (aOR 3.17, 95% CI 1.03-9.69). An elevated CRP level was associated with a shorter PPROM to delivery latency (adjusted B -16.64, 95% CI -29.88 to -3.41), but cerclage retention more than 12 hours after PPROM was associated with a prolonged latency (adjusted B 17.21, 95% CI 3.25-31.18). CONCLUSION: Oligohydramnios and chorioamnionitis are associated with neonatal mortality.


Assuntos
Ruptura Prematura de Membranas Fetais/epidemiologia , Nascimento Prematuro/prevenção & controle , Incompetência do Colo do Útero/cirurgia , Adulto , Cerclagem Cervical/estatística & dados numéricos , Corioamnionite/mortalidade , Feminino , Ruptura Prematura de Membranas Fetais/mortalidade , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Oligo-Hidrâmnio/mortalidade , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/metabolismo , Estudos Retrospectivos , Fatores de Risco , Taiwan
11.
Food Chem Toxicol ; 132: 110700, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31356917

RESUMO

Postnatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, is associated with allergy development in childhood, suggesting that DEHP exposure may dysregulate immune response in infants. We investigated whether DEHP exposure in newborns through medical treatment affected the gut microbiota pattern and vaccine response, which are both related to immune development. In this prospective cohort study from May 1, 2016 through July 31, 2017, newborns with respiratory distress who were given intravenous infusions (IVs) were enrolled as the DEHP group, and newborns who did not receive IVs were enrolled as the control group. We excluded patients with perinatal maternal probiotics, vaginal delivery, antibiotic treatment, and exclusive human milk or formula feeding. Of 118 infants, urinary phthalate metabolite analysis revealed that the calculated DEHP concentrations of the newborns treated with IVs (n = 15) were higher than those in the control group (n = 10) (p = 0.0001). DEHP exposure altered bacterial communities both in composition and diversity, particularly decreases in Rothia sp. and Bifidobacterium longum in the DEHP group. Furthermore, DEHP exposure significantly enhanced anti-HBsAg-IgM responses in the DEHP group (p = 0.013). Early-life DEHP exposure alter gut microbiota of newborns and may change their immune responses in later life.


Assuntos
Dietilexilftalato/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Vacinas contra Hepatite B/administração & dosagem , Imunoglobulina M/sangue , Plastificantes/farmacologia , Dietilexilftalato/urina , Feminino , Hidratação , Humanos , Imunoglobulina M/imunologia , Recém-Nascido , Infusões Intravenosas , Masculino , Plastificantes/análise
12.
Opt Lett ; 44(4): 1027-1030, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30768047

RESUMO

Dark-field microscopy is widely used to image micro/nano particles or characterize their optical response (scattering spectrum). If laser excitation is incorporated into the microscope, the microscope can further probe chemical (molecular) properties of these objects through Raman scattering. However, when the size of the particles is comparable to or smaller than the characteristic sizes of the laser beam, the conventional setup using on-axis excitation usually suffers from undesired background signals produced by illuminated substrates below the target particles. Therefore, a crescent laser beam possessing a stable shape along the propagation direction is generated by a pair of shifted axicons and then integrated into a dark-field microscope for large oblique angle (i.e., off-axis) excitation. Under this excitation setup, the contrast between Raman and background fluorescence spectra is enhanced by a factor of 4 for a 1 µm polystyrene particle sitting on a glass slide, compared to the conventional excitation configuration. This off-axis excitation based on the crescent beam integrates dark-field imaging with Raman spectroscopy and improves Raman characterization of micro/nano particles.

13.
Eur J Clin Microbiol Infect Dis ; 38(2): 365-372, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30460416

RESUMO

This study aimed to investigate the association between herpes zoster (HZ) and the risks of osteoporosis and fracture. We conducted a nationwide retrospective cohort study using the National Health Insurance Research Database of Taiwan. The study enrolled 63,786 patients: 31,893 diagnosed with HZ between 2000 and 2012 were included in the HZ cohort, and 31,893 matched controls without HZ were included in the non-HZ cohort, with 1:1 exact matching for age, sex, and index year. Hazard ratios (HRs) were calculated for the risks of osteoporosis and fracture according to the HZ status using the Cox proportional hazards regression models. During a mean follow-up period of 6.0 years, 5597 and 4639 patients in the HZ and non-HZ cohorts, respectively, developed osteoporosis or fractures (incidence rate: 29.8 vs. 23.8 per 1000 person-years). HZ diagnosis was significantly associated with an elevated risk of developing osteoporosis or fracture (adjusted HR [aHR] = 1.20, p < 0.001). On analyses for each individual event, the HZ cohort had significantly increased risks for all events, including osteoporosis (aHR = 1.32, p < 0.001), hip fracture (aHR = 1.34, p < 0.001), vertebral fracture (aHR = 1.38, p < 0.001), and other fractures (aHR = 1.10, p < 0.001) compared with the non-HZ cohort. Patients with postherpetic neuralgia had especially higher risks of osteoporosis and fracture. Age- and sex-stratified analyses also revealed similar patterns. In conclusion, HZ was independently associated with an increased risk of osteoporosis and fracture. Further studies are required to investigate its underlying mechanisms.


Assuntos
Fraturas Ósseas/epidemiologia , Herpes Zoster/epidemiologia , Osteoporose/epidemiologia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Seguimentos , Herpes Zoster/diagnóstico , Herpesvirus Humano 3/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Taiwan/epidemiologia
14.
Biomed Pharmacother ; 107: 19-23, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30075369

RESUMO

Paeoniflorin (PF) is one of the important active components in peony that are known to produce the neuroprotective effects. However, the involved cytoprotective factors on brain astrocytes are remain unclear. Translocator protein 18 kDa (TSPO) and its downstream neurosteroids biosynthesis play a significant role in cytoprotection. Based on these, the role of TSPO and neurosteroids biosynthesis in the cytoprotective effects of PF is evaluated. The astrocyte cells were cultured and AC-5216 (TSPO ligand) was selected as the positive control drug. The cytoprotective effects of PF and the levels of neurosteroids were quantified by water-soluble tetrazolium assay and enzyme linked immunosorbent assay, respectively. The cytoprotective activities of PF were relevant to neurosteroids (e.g. progsterone and allopregnanolone) biosynthesis, while these effects were totally blocked by PK11195, trilostane and finasteride, respectively. In summary, the cytoprotective effects of PF maybe mediated by TSPO and neurosteroids biosynthesis. The findings may provide the new insights into the cytoprotective effects of PF.


Assuntos
Proteínas de Transporte/metabolismo , Citoproteção , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Substâncias Protetoras/farmacologia , Receptores de GABA-A/metabolismo , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Linhagem Celular , Citoproteção/efeitos dos fármacos , Isoquinolinas , Ratos , Esteroides/farmacologia
15.
Vet Comp Oncol ; 16(4): 670-676, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30129270

RESUMO

C-met is a receptor normally expressed on epithelial cells and dysregulated in human breast cancers. Mammary tumours are the most common tumour in female dogs. The aims of this study were to detect the expression of c-met in canine mammary tumours (CMTs) and evaluate the correlations between c-met expression and clinicopathological features. A total of 240 specimens of canine mammary tissues composed of 30 normal glands, 30 hyperplastic ones, 90 benign tumours and 90 carcinomas obtained from 127 bitches were examined by immunohistochemical staining. Positive c-met immunoreactivity was demonstrated in the cytoplasm of mammary epithelial cells at variable levels, and in malignant CMTs, higher c-met expression was found in carcinomas whose grade, stage and mitotic index were low, and metastasis was absent. The median survival time was shorter in dogs with malignant CMTs with a maximum diameter ≥5 cm, regional lymph node or distant metastasis, and a high histologic grade. However, the 2-year survival rate was higher in dogs with malignant CMTs of higher c-met expression than those of low c-met expression (80.1% vs 57%). C-met expression could be used as a valuable positive prognostic factor for the clinical outcomes of dogs with malignant CMTs.


Assuntos
Doenças do Cão/diagnóstico , Neoplasias Mamárias Animais/diagnóstico , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Doenças do Cão/metabolismo , Doenças do Cão/mortalidade , Doenças do Cão/patologia , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/mortalidade , Neoplasias Mamárias Animais/patologia , Prognóstico
16.
Front Immunol ; 8: 1508, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29184551

RESUMO

Interleukin-4 (IL-4) has been considered as one of the tolerogenic cytokines in many autoimmune animal models and clinical settings. Despite its role in antagonizing pathogenic Th1 responses, little is known about whether IL-4 possesses functions that affect regulatory T cells (Tregs). Tregs are specialized cells responsible for the maintenance of peripheral tolerance through their immune modulatory capabilities. Interestingly, it has been suggested that IL-4 supplement at a high concentration protects responder T cells (Tresps) from Treg-mediated immune suppression. In addition, such supplement also impedes TGF-ß-induced Treg differentiation in vitro. However, these phenomena may contradict the tolerogenic role of IL-4, and the effects of IL-4 on Tregs are therefore needed to be further elucidated. In this study, we utilized IL-4 knockout (KO) mice to validate the role of IL-4 on Treg-mediated immune suppression. Although IL-4 KO and control animals harbor similar frequencies of Tregs, Tregs from IL-4 KO mice weakly suppressed autologous Tresp activation. In addition, IL-4 deprivation impaired the ability of Tregs to modulate immune response, whereas IL-4 supplementation reinforced IL-4 KO Tregs in their function in suppressing Tresps. Finally, the presence of IL-4 was associated with increased cell survival and granzyme expression of Tregs. These results suggest the essential role of IL-4 in supporting Treg-mediated immune suppression, which may benefit the development of therapeutic strategies for autoimmune diseases.

17.
Cell Physiol Biochem ; 41(4): 1661-1674, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28359056

RESUMO

OBJECTIVE: The present study aimed to establish an induced pluripotent stem cell (iPSC) line from acute myelogenous leukemia (AML) cells in vitro and identify their biological characteristics. METHODS: Cells from the AML-infiltrated skin from an M6 patient were infected with a lentivirus carrying OCT4, SOX2, KLF4 and C-MYC to induce iPSCs. The characteristics of the iPSCs were confirmed by alkaline phosphatase (ALP) staining. The proliferation ability of iPSCs was detected with a CCK-8 assay. The expression of pluripotency markers was measured by immunostaining, and the expression of stem cell-related genes was detected by qRT-PCR; distortion during the induction process was detected by karyotype analysis; the differentiation potential of iPSCs was determined by embryoid body-formation and teratoma-formation assays. ALP staining confirmed that these cells exhibited positive staining and had the characteristics of iPSCs. RESULTS: The CCK-8 assay showed that the iPSCs had the ability to proliferate. Immunostaining demonstrated that iPSC clones showed positive expression of NANOG, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. qRT-PCR results revealed that the mRNA expression of Nanog, Lin28, Cripto, FOX3, DNMT3b, DPPA2, and DPPA4 significantly increased in iPSCs. Karyotype analysis found no chromosome aberration in the iPSCs. The results of the embryoid body-formation and teratoma-formation assays indicated that the iPSCs had the potential to differentiate into all three germ layers. CONCLUSION: Our study provided evidence that an iPSC line derived from AML cells was successfully established.


Assuntos
Regulação Leucêmica da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucemia Eritroblástica Aguda/metabolismo , Proteínas de Neoplasias/biossíntese , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição/biossíntese , Adulto , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patologia , Masculino , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Fatores de Transcrição/genética
18.
Mediators Inflamm ; 2017: 3082805, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28255203

RESUMO

Indirubin is a Chinese medicine extracted from indigo and known to be effective for treating chronic myelogenous leukemia, neoplasia, and inflammatory disease. This study evaluated the in vivo anti-inflammatory activity of indirubin in a lipopolysaccharide- (LPS-) induced mouse mastitis model. The indirubin mechanism and targets were evaluated in vitro in mouse mammary epithelial cells. In the mouse model, indirubin significantly attenuated the severity of inflammatory lesions, edema, inflammatory hyperemia, milk stasis and local tissue necrosis, and neutrophil infiltration. Indirubin significantly decreased myeloperoxidase activity and downregulated the production of tumor necrosis factor-α, interleukin-1ß (IL-1ß), and IL-6 caused by LPS. In vitro, indirubin inhibited LPS-stimulated expression of proinflammatory cytokines in a dose-dependent manner. It also downregulated LPS-induced toll-like receptor 4 (TLR4) expression and inhibited phosphorylation of LPS-induced nuclear transcription factor-kappa B (NF-κB) P65 protein and inhibitor of kappa B. In addition to its effect on the NF-κB signaling pathway, indirubin suppressed the mitogen-activated protein kinase (MAPK) signaling by inhibiting phosphorylation of extracellular signal-regulated kinase (ERK), P38, and c-jun NH2-terminal kinase (JNK). Indirubin improved LPS-induced mouse mastitis by suppressing TLR4 and downstream NF-κB and MAPK pathway inflammatory signals and might be a potential treatment of mastitis and other inflammatory diseases.


Assuntos
Lipopolissacarídeos/toxicidade , Glândulas Mamárias Humanas/metabolismo , Mastite/induzido quimicamente , Mastite/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Indóis/uso terapêutico , Interleucina-1beta/metabolismo , Interleucina-3/metabolismo , Interleucina-6/metabolismo , Masculino , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/patologia , Mastite/metabolismo , Camundongos , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Mol Med Rep ; 15(4): 2143-2153, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28260062

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by islet ß-cell dysfunction and insulin resistance, which leads to an inability to maintain blood glucose homeostasis. Circulating microRNAs (miRNAs) have been suggested as novel biomarkers for T2DM prediction or disease progression. However, miRNAs and their roles in the pathogenesis of T2DM remain to be fully elucidated. In the present study, the serum miRNA expression profiles of T2DM patients in Chinese cohorts were examined. Total RNA was extracted from serum samples of 10 patients with T2DM and five healthy controls, and these was used in reverse-transcription­quantitative polymerase chain reaction analysis with the Exiqon PCR system of 384 serum/plasma miRNAs. A total of seven miRNAs were differentially expressed between the two groups (fold change >3 or <0.33; P<0.05). The serum expression levels of miR­455­5p, miR­454­3p, miR­144­3p and miR­96­5p were higher in patients with T2DM, compared with those of healthy subjects, however, the levels of miR­409­3p, miR­665 and miR­766­3p were lower. Hierarchical cluster analysis indicated that it was possible to separate patients with T2DM and control individuals into their own similar categories by these differential miRNAs. Target prediction showed that 97 T2DM candidate genes were potentially modulated by these seven miRNAs. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 24 pathways were enriched for these genes, and the majority of these pathways were enriched for the targets of induced and repressed miRNAs, among which insulin, adipocytokine and T2DM pathways, and several cancer­associated pathways have been previously associated with T2DM. In conclusion, the present study demonstrated that serum miRNAs may be novel biomarkers for T2DM and provided novel insights into the pathogenesis of T2DM.


Assuntos
Diabetes Mellitus Tipo 2/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Idoso , China/epidemiologia , Análise por Conglomerados , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Regulação da Expressão Gênica , Genômica , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade
20.
Org Biomol Chem ; 15(9): 2020-2032, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28203674

RESUMO

An efficient and low-cost method for the synthesis of 4-substituted quinolin-2-(1H)-ones has been developed. In the presence of TBHP, the cobalt(ii)-catalyzed carbocyclization reactions of arylethenyl substituted α-bromo-N-phenylacetamides, involving sequential 6-exo-trig radical cyclization, t-butylperoxy radical cross-coupling reaction and the base-promoted ionic Kornblum-DeLaMare reaction, produced 4-benzoylquinolin-2-(1H)-ones. A variety of useful functional groups such as methoxy, fluoro, chloro, bromo, methoxycarbonyl, and cyano groups, are compatible with the reaction conditions. This strategy was further applied to arylethynyl substituted α-bromo-N-phenylacetamides, and 4-benzylquinolin-2-(1H)-ones were formed effectively.

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