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1.
Ann Med ; 56(1): 2391019, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39155824

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.


High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.


Assuntos
Ciclosporina , Quimioterapia Combinada , Síndromes do Olho Seco , Humanos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adulto , Índice de Gravidade de Doença , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos
2.
J Cell Mol Med ; 28(15): e18586, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39121240

RESUMO

Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.


Assuntos
Movimento Celular , Chalconas , Metaloproteinase 2 da Matriz , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Invasividade Neoplásica , Fator de Transcrição STAT3 , Transdução de Sinais , Humanos , Fator de Transcrição STAT3/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Chalconas/farmacologia , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Transdução de Sinais/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
Diagnostics (Basel) ; 14(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39001240

RESUMO

In this study, we aimed to evaluate the association between the severity of coronary heart disease (CHD) and the subsequent severity of blepharitis. This retrospective population-based cohort study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. The participants with a CHD diagnosis were divided into mild CHD and severe CHD groups at a 1:2 ratio, according to whether percutaneous coronary intervention (PCI) was performed. The main outcomes were the development of blepharitis and severe blepharitis with the application of antibiotics. Cox proportional hazard regression was performed to obtain the adjusted hazard ratio (aHR) for blepharitis, with a 95% confidence interval (CI) between the groups. There were 22,161 and 15,369 blepharitis events plus 9597 and 4500 severe blepharitis episodes in the mild and severe CHD groups, respectively. The severe CHD group showed a significantly higher incidence of blepharitis development (aHR, 1.275; 95% CI: 1.051-1.912, p = 0.0285), whereas the incidence of severe blepharitis was not significantly different between the groups (aHR, 0.981; 95% CI: 0.945-1.020, p = 0.3453). The cumulative probability of blepharitis was significantly higher in the severe CHD group than in the mild CHD group (p < 0.001). In the subgroup analyses, the correlation between severe CHD and blepharitis was more significant in patients older than 70 years compared to the younger group (p = 0.0115). In conclusion, severe CHD is associated with a higher incidence of blepharitis than mild CHD, and this correlation is more prominent in individuals older than 70 years.

4.
Int J Mol Sci ; 25(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39063157

RESUMO

Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future.


Assuntos
Apoptose , Quinolinas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Quinolinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Células HeLa , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Endogâmicos BALB C , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos
5.
Life (Basel) ; 14(7)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39063559

RESUMO

We aimed to evaluate the postoperative visual and refractive outcomes between the first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries. A retrospective cohort study was conducted and patients who had received first- and second-generation KLEx surgeries were enrolled. A total of 80 and 80 eyes were categorized into the first and second KLEx groups after exclusion, respectively. The primary outcomes were the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and safety indexes. An independent t-test and generalized estimate equation were implemented to compare the primary outcomes between the two groups. After the KLEx surgery, the UDVA showed no significant difference between the two groups throughout the study period (all p > 0.05), and the postoperative SE and safety index were also statistically identical between the two groups during the follow-up interval (all p > 0.05). There was a similar trend of visual recovery between the two groups (aOR: 0.967; 95% CI: 0.892-1.143; p = 0.844), while the amplitude of the SE change was significantly lower in the second KLEx group (aOR: 0.760; 95% CI: 0.615-0.837; p = 0.005). Nine and two unintended initial dissection of the posterior plane (UIDPP) occurred intraoperatively in the first and second KLEx groups, respectively, and the second group showed a lower risk of UIDPP (p = 0.032). In conclusion, the efficiency, predictability, and safety are similar between first- and second-generation KLEx surgeries.

6.
Diagnostics (Basel) ; 14(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39061636

RESUMO

We aim to investigate the potential risk factors for undercorrection in those who have received extend depth-of-focus (EDOF) intraocular lens (IOL) implantation. A retrospective case-control study was conducted in which patients who had received one type of EDOF IOL implantation were included. The patients were divided into the residual group and non-residual group according to the final postoperative sphere power. The preoperative data include the refractive, topographic, endothelial, and biometric parameters obtained. A generalized linear model was generated to yield the adjusted odds ratio (aOR) and 95% confidence interval (CI) of each parameter of the residual myopia. One month postoperatively, the UDVA was better in the non-residual group than in the residual group (p = 0.010), and the final SE was significantly higher in the residual group than in the non-residual group (p < 0.001). In the multivariable analysis, the high preoperative cycloplegia sphere power, higher TCRP, higher corneal cylinder power, and longer AXL significantly correlated to the presence of postoperative residual myopia (all p < 0.05). Furthermore, the higher preoperative cycloplegia sphere power, higher TCRP, higher corneal cylinder power, longer AXL, larger ACD, and larger WTW were significantly associated with postoperative residual myopia in the high-myopia population (all p < 0.001), while the higher preoperative cycloplegia sphere power, higher TCRP, and longer AXL were related to postoperative residual myopia in the low-myopia population (all p < 0.05). In conclusion, high preoperative myopia and corneal refractive power correlate to high risk of residual myopia after EDOF IOL implantation, especially in the high-myopia population.

8.
Eur J Ophthalmol ; : 11206721241266704, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39056133

RESUMO

AIM: We attempted to test the influences of cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms on the susceptibility to Diabetic retinopathy (DR). METHODS: Five single-nucleotide polymorphisms (SNPs) of the CDKN2B-AS1 gene, rs564398, rs1333048, rs1537373, rs2151280, and rs8181047 were examined in 280 DR cases and 455 DR-free diabetic controls. RESULTS: Among these loci tested, we demonstrated that diabetic carriers of at least one polymorphic allele (G) of rs2151280 (AG and GG; AOR, 1.613; 95% CI, 1.040-2.501; p = 0.033) are more susceptible to proliferative DR but not non-proliferative DR. This genetic association with the risk of developing proliferative DR was further strengthened in homozygotes for the polymorphic allele (G) of rs2151280 (GG; AOR, 2.194; 95% CI, 1.117-4.308; p = 0.023). We detected a significant association of the polymorphic allele (G) of rs2151280 with proliferative DR patients (OR, 1.503; 95% CI, 1.112-2.033; p = 0.008) but not with the entire DR or non-proliferative DR group. Moreover, as compared to those who do not possess the polymorphic allele of rs2151280 (AA), DR patients carrying at least one polymorphic allele of rs2151280 (AG + GG) exhibited a lower glomerular filtration rate and HDL cholesterol level, revealing a promotive role of rs2151280 in renal and cardiovascular complications of diabetes. CONCLUSION: Taken together, our findings implicate an impact of CDKN2B-AS1 gene polymorphisms on the progression of DR.

9.
Int J Med Sci ; 21(8): 1408-1413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903923

RESUMO

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias do Endométrio , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias do Endométrio/epidemiologia , Pessoa de Meia-Idade , Incidência , Taiwan/epidemiologia , Estudos Retrospectivos , Idoso , Adulto
10.
Int J Med Sci ; 21(8): 1428-1437, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903932

RESUMO

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.


Assuntos
Predisposição Genética para Doença , Receptores de Hialuronatos , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Receptores de Hialuronatos/genética , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Taiwan/epidemiologia , Genótipo , Idoso , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/mortalidade , Metástase Linfática/genética , Metástase Linfática/patologia
11.
Diagnostics (Basel) ; 14(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38928627

RESUMO

The risk of developing cardiovascular disease is significantly higher for individuals with diabetes compared to those without. Aspirin has been widely used for primary prevention in diabetic patients. However, evidence is limited in the Asian population. We aimed to compare the effectiveness and safety of aspirin versus placebo for primary cardiovascular prevention in the Asian population with type 2 diabetes. In this study, we performed propensity score matching with non-aspirin users from January 2006 to December 2015 (n = 37,095 in each group after matching, PSM). We analyzed the incidence risk of all-cause mortality, composite cardiovascular events, and hospitalized major bleeding. The propensity score-matched (PSM) cohort of patients who received aspirin within one year of diabetes diagnosis was compared with the non-aspirin diabetic (DM) cohort. Baseline characteristics were balanced between the two groups. The median follow-up duration was 78 months. Aspirin users exhibited a slightly but significantly lower rate of all-cause mortality (HR: 0.92; 95% CI: 0.87 to 0.96). However, they also had a significantly higher composite cardiovascular risk (HR: 1.34; 95% CI: 1.28-1.40), including non-fatal acute myocardial infarction (HR: 1.33; 95% CI: 1.18 to 1.50), non-fatal ischemic stroke (HR: 1.38; 95% CI: 1.30 to 1.45), heart failure (HR: 1.18; 95% CI: 1.09 to 1.27), and coronary revascularization (HR: 1.94; 95% CI: 1.73 to 2.17). Aspirin users also faced a significantly higher risk of hospitalized major bleeding (HR: 1.08; 95% CI: 1.03 to 1.14). The presence of one or more additional risk factors did not influence the effectiveness and safety outcomes of aspirin, according to stratified analysis. In conclusion, in this real-world Asian diabetic population, aspirin was associated with a significantly lower mortality risk but also with higher risks of cardiovascular events and hospitalized bleeding. Aspirin may not play a role in the primary prevention of cardiovascular disease in such patients, regardless of additional risk factors.

12.
Diagnostics (Basel) ; 14(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38928690

RESUMO

Our objective was to evaluate the topographic and surgical factors of early myopic regression between laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). A retrospective case-control study was conducted, and 368 and 92 eyes were enrolled in the LASIK and SMILE groups via propensity score matching (PSM). Visual acuity, refractive status, axial length, and topographic/surgical parameters were collected. Multiple linear regression was applied to the yield coefficient and the 95% confidence interval (CI) of the parameters. The cumulative incidence of early myopic regression was higher in the LASIK group (p < 0.001). In the SMILE group, a lower central corneal thickness (CCT) thinnest value and a higher corneal cylinder associated with early myopic regression were observed; meanwhile, in the LASIK group, a lower CCT thinnest value, a higher steep corneal curvature, a larger optic zone, and a lower flap thickness related to early myopic regression were observed (all p < 0.05). In the SMILE group, a higher CCT difference correlated with early myopic regression was observed compared to the LASIK group (p = 0.030), and higher steep corneal curvature and lower cap/flap thickness (both p < 0.05) correlated with early myopic regression were observed in the LASIK group compared to the SMILE group. In conclusion, CCT differences significantly influence early myopic regression in the SMILE group; meanwhile, corneal curvature and flap thickness affect early myopic regression principally in the LASIK group.

13.
Cancers (Basel) ; 16(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38927988

RESUMO

Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.

14.
Eur J Pharmacol ; 977: 176676, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38815787

RESUMO

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.


Assuntos
Apoptose , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Fibrose , Flavanonas , Obstrução Ureteral , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Obstrução Ureteral/complicações , Obstrução Ureteral/patologia , Obstrução Ureteral/tratamento farmacológico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Apoptose/efeitos dos fármacos , Masculino , Camundongos , Linhagem Celular , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Fator de Crescimento Transformador beta/metabolismo , Ratos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Camundongos Endogâmicos C57BL
15.
J Affect Disord ; 358: 205-210, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38729220

RESUMO

STUDY OBJECTIVE: To explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management. DESIGN: A nested case-control study utilizing data from a longitudinal health insurance database. SETTING: The study is based on a longitudinal health insurance database spanning 2000-2019 in Taiwan. PATIENTS: A total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis. INTERVENTION: Analysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls. MEASUREMENT: Data included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk. MAIN RESULTS: No significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83-1.01), indicating no substantial increase in risk. CONCLUSION: Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential.


Assuntos
Analgésicos , Dor Crônica , Demência , Gabapentina , Humanos , Gabapentina/efeitos adversos , Feminino , Masculino , Estudos de Casos e Controles , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Idoso , Demência/epidemiologia , Demência/induzido quimicamente , Pessoa de Meia-Idade , Taiwan/epidemiologia , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Idoso de 80 Anos ou mais , Fatores de Risco
16.
Arch Med Sci ; 20(2): 402-409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38757017

RESUMO

Introduction: To survey the potential correlation between the application of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the incidence of uveitis in individuals with type 2 diabetes mellitus (T2DM). Material and methods: A retrospective cohort study using the National Health Insurance Research Database (NHIRD) was conducted. The T2DM patients using SGLT2 inhibitors and those taking other anti-diabetic medications were assigned to the SGLT2 group and the control group, respectively, with a 1 : 2 ratio via the propensity score-matching (PSM) method. The major outcome in this study is the development of uveitis according to the diagnostic codes. The Cox proportional hazard regression was adopted to yield the adjusted hazard ratio (aHR) with 95% confidence interval (CI) between the groups. Results: There were 147 and 371 new uveitis episodes in the SGLT2 and control groups after the follow-up period up to 5 years. The incidence of uveitis in the SGLT2 group (aHR = 0.736, 95% CI: 0.602-0.899, p = 0.0007) was significantly lower than that in the control group after adjusting for the effect of all the confounders. In the subgroup analyses, the SGLT2 inhibitors showed a higher correlation with low uveitis incidence in T2DM patients aged under 50 than T2DM individuals aged over 50 years (p = 0.0012), while the effect of SGLT2 inhibitors on the incidence of anterior and posterior uveitis development was similar (p = 0.7993). Conclusions: The use of SGLT2 inhibitors could be an independent protective factor for uveitis development in T2DM population.

17.
Invest Ophthalmol Vis Sci ; 65(5): 37, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38780946

RESUMO

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.


Assuntos
Biometria , Endotélio Corneano , Idade Gestacional , Recém-Nascido Prematuro , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Recém-Nascido , Endotélio Corneano/patologia , Refração Ocular/fisiologia , Contagem de Células , Lactente , Pré-Escolar , Comprimento Axial do Olho/patologia , Criança
18.
Curr Eye Res ; 49(9): 980-987, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38717215

RESUMO

PURPOSE: This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of maternally expressed gene 3 (MEG3) and the clinical manifestations of diabetic retinopathy (DR). METHODS: Five loci of MEG3 SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals. RESULTS: The distribution frequency of MEG3 SNP rs7158663 GA (AOR: 0.683, 95% CI: 0.478-0.975, p = 0.036) and MEG3 SNP rs7158663 GA + AA (AOR: 0.686, 95% CI: 0.487-0.968, p = 0.032) were significantly lower in the DR group. And the MEG3 SNP rs7158663 GA + AA (AOR: 0.610, 95% CI: 0.377-0.985, p = 0.043) demonstrated a significantly lower distribution frequency in the male DR group. Besides, the DR patients with MEG3 SNP rs7158663 GA + AA genotype showed a significantly lower HbA1c level than the DR patients with MEG3 SNP rs7158663 GG genotype (7.29 ± 1.23 versus 7.74 ± 1.49, p = 0.013). Moreover, in the analysis using data from gene expression data series database, a higher MEG3 level was significantly correlated to a lower miR-182 level in the database (p = 0.0114). CONCLUSIONS: In this study, the distribution frequency of MEG3 SNP rs7158663 GA + AA genotype was lower in DR, while the DR would develop under lower HbA1c level in DM patients with this MEG3 SNP variant.


Assuntos
Retinopatia Diabética , Genótipo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Humanos , Retinopatia Diabética/genética , Retinopatia Diabética/diagnóstico , RNA Longo não Codificante/genética , Masculino , Feminino , Pessoa de Meia-Idade , Predisposição Genética para Doença , Frequência do Gene , Idoso , Alelos , Hemoglobinas Glicadas/metabolismo
19.
Int J Med Sci ; 21(7): 1329-1336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818477

RESUMO

Purpose: The purpose of this study was to compare the differences in myopic control effects between orthokeratology (OK) contact lenses and defocus incorporated multiple segments (DIMS) spectacle lenses. Methods: A retrospective cohort study was conducted that included patients who had received OK lens, DIMS spectacle lens or single-vision spectacle treatments. A total of 54 eyes from 27 individuals, 38 eyes from 19 individuals and 42 eyes from 21 individuals were enrolled into the OK lens, DIMS and control groups, respectively. The primary outcomes were the changes in the spherical equivalent refraction (SER) and axial length (AXL) among the groups. A repeated-measure ANCOVA was adopted to calculate the SER progression and AXL elongation of the OK lens group compared with the DIMS group. Results: The difference in the SER progression was clinically non-significant in the OK lens group compared with the DIMS and control groups (P = 0.001). The total AXL elongation results were similar between the OK lens and DIMS groups, but these were lower than in the control group (P = 0.005). The repeated-measure ANCOVA revealed that the SER progression difference during the study interval was clinically non-significant in the OK lens group when compared with the DIMS group (P = 0.028). The AXL elongation results between the OK lens and DIMS populations did not illustrate a significant difference (P = 0.607). In a subgroup analysis of moderate astigmatism, better AXL control was observed in the DIMS subgroup compared with the OK lens subgroup (P = 0.016). Conclusions: The OK lens demonstrated a clinically non-significant effect on the SER and AXL controls compared with the DIMS spectacle lens.


Assuntos
Óculos , Miopia , Procedimentos Ortoceratológicos , Refração Ocular , Humanos , Miopia/terapia , Miopia/fisiopatologia , Masculino , Feminino , Procedimentos Ortoceratológicos/métodos , Estudos Retrospectivos , Refração Ocular/fisiologia , Adulto , Lentes de Contato , Adulto Jovem , Adolescente , Acuidade Visual , Resultado do Tratamento
20.
Environ Toxicol ; 39(9): 4308-4317, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38717057

RESUMO

Deoxyshikonin (DSK) is a biological component derived from Lithospermum erythrorhizon. Although DSK possesses potential anticancer activities, whether DSK exerts anticancer effects on cervical cancer cells is incompletely explored. This study was aimed to investigate the anticancer activity of DSK against cervical cancer cells and its molecular mechanisms. Cell viability was evaluated by MTT assay. Level of phosphorylation and protein was determined using Western blot. Involvement of signaling kinases was assessed by specific inhibitors. Our results revealed that DSK reduced viability of human cervical cell in a dose-dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa and SiHa cells. Apoptosis microarray was used to elucidate the involved pathways, and the results showed that DSK dose-dependently diminished cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-8/9/3. Furthermore, we observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK (p38), and only inhibition of p38 diminished the DSK-mediated pro-caspases cleavage. Taken together, our results demonstrate that DSK has anti-cervical cancer effects via the apoptotic cascade elicited by downregulation of IAPs and p38-mediated caspase activation. This suggests that DSK could act as an adjuvant to facilitate cervical cancer management.


Assuntos
Apoptose , Caspases , Neoplasias do Colo do Útero , Proteínas Quinases p38 Ativadas por Mitógeno , Humanos , Apoptose/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/tratamento farmacológico , Feminino , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células HeLa , Lithospermum/química , Antineoplásicos/farmacologia , Naftoquinonas/farmacologia , Antraquinonas/farmacologia , Ativação Enzimática/efeitos dos fármacos
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