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1.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542323

RESUMO

As the global population ages, the number of patients with osteoporosis is rapidly rising. The existing first-line clinical drugs are bone resorption inhibitors that have difficulty restoring the bone mass of elderly patients to the safe range. The range and period of use of existing peptides and monoclonal antibodies are limited, and small-molecule bone formation-promoting drugs are urgently required. We established an I-9 synthesis route with high yield, simple operation, and low cost that was suitable for future large-scale production. I-9 administration promoted bone formation and increased bone mass in mice with low bone mass in an aged C57 mouse model. Our findings revealed a hitherto undescribed pathway involving the BMP2-ERK-ATF4 axis that promotes osteoblast differentiation; I-9 has favorable biosafety in mice. This study systematically investigated the efficacy, safety, and mechanism of I-9 for treating osteoporosis and positions this drug for preclinical research in the future. Thus, this study has promoted the development of small-molecule bone-promoting drugs.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Idoso , Camundongos , Humanos , Animais , Osteogênese , Preparações Farmacêuticas/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Peptídeos/metabolismo , Diferenciação Celular , Osteoblastos/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Proteína Morfogenética Óssea 2/metabolismo
2.
Biochem Biophys Res Commun ; 656: 86-96, 2023 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-36958259

RESUMO

The abnormal immune response mediated by malignant melanoma is related to PD1. Paeonol has pharmacological antitumor activity. Previous studies have indicated that paeonol induces tumor cell apoptosis, but its underlying mechanism in tumor immunity remains unknown. In this study, malignant melanoma was established in normal and thymectomized mice to determine the important role of the thymus in the antitumor effects of paeonol. Paeonol-treated thymocytes were cocultured with melanoma cell spheres to further evaluate the regulatory role of thymocytes in tumor immune dysfunction. Studies have shown that PD1 may be targeted by miR-139-5p. Our results revealed that tumor-induced thymic atrophy was significantly accompanied by high PD1 expression and low miR-139-5p expression. Interestingly, paeonol significantly reversed thymic atrophy and largely protected thymocytes against low PD1 expression and high miR-139-5p expression. Dual-luciferase assays indicated that miR-139-5p interacted with the 3' untranslated region (3'-UTR) of PD1. These results showed that paeonol alleviates PD1-mediated antitumor immunity by reducing miR-139-5p expression and demonstrated a novel mechanism for melanoma immunotherapy.


Assuntos
Melanoma , MicroRNAs , Animais , Camundongos , Regulação para Cima , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Apoptose , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Melanoma Maligno Cutâneo
3.
Graefes Arch Clin Exp Ophthalmol ; 261(1): 127-135, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35802204

RESUMO

PURPOSE: To investigate the characteristics of eyes with large variations in predicted refraction using four traditional intraocular lens (IOL) formulas and evaluate the accuracy of new-generation intraocular lens power calculation formulas. METHODS: Eyes that had variation in predicted refraction (≥ 0.75 D) using four traditional formulas (SRK/T, Holladay 1, Hoffer Q, and Haigis formulas) were included. Axial length (AL), anterior chamber depth (ACD), average keratometry (AK), and the ratio of axial length to corneal radius (AL/CR) were measured. New-generation formulas (Barrett Universal II, Emmetropia Verifying Optical 2.0, Kane, and Pearl-DGS formulas) and traditional formulas were compared. The median absolute error (MedAE) was the main parameter to evaluate the accuracy of formulas. RESULTS: A total of 79 participants (79 eyes) who had variation in predicted refraction of (≥ 0.75 D) using four traditional formulas out of 510 eyes (510 patients) underwent uncomplicated cataract surgeries. The Barrett Universal II (0.29 D), EVO 2.0 (0.31 D), Kane (0.30 D), and Pearl-DGS (0.33 D) formulas produced significantly lower median absolute errors (MedAEs) than the Hoffer Q (0.61 D) and Holladay 1 (0.59 D) formulas (P < 0.01). The Wang-Koch (WK) adjustment significantly improved the accuracy of the Holladay 1 formula in long eyes (P < 0.001). CONCLUSIONS: Abnormal AL, ACD, and AK are more likely to lead to prediction errors using traditional formulas. New-generation formulas and traditional formulas with WK adjustment showed satisfactory prediction accuracy.


Assuntos
Lentes Intraoculares , Facoemulsificação , Humanos , Acuidade Visual , Implante de Lente Intraocular , Refração Ocular , Testes Visuais , Biometria , Estudos Retrospectivos , Óptica e Fotônica , Comprimento Axial do Olho
4.
Health Commun ; 38(5): 1022-1032, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-34665071

RESUMO

While health communication campaigns seek to encourage and promote healthy behaviors, they are not always successful. Health communication efforts may fail for several reasons, such as viewers experiencing excessive freedom threats and reactance. This study (n = 201) proposes and demonstrates that descriptive norm appeals in health PSAs can indirectly lead to enhanced behavioral intentions toward the message advocacy via reducing perceived freedom threats, inhibiting psychological reactance, and improving message credibility. However, this serial mediation was only found for message viewers with relatively low media literacy skills - precisely, who did not show considerable critical thinking toward media content. For participants who reported a high level of critical thinking toward media content, the use of descriptive norm appeals did not decrease freedom threats, nor did it indirectly affect behavioral intentions. The findings of this study contribute to the theory of psychological reactance and norms-based research. Both theoretical and practical implications are provided for health communication scholars and practitioners.


Assuntos
Comunicação em Saúde , Alfabetização , Humanos , Publicidade , Teoria Psicológica , Liberdade , Intenção
5.
Health Commun ; : 1-13, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572549

RESUMO

Families play an important role in addressing substance misuse and addiction. Extant literature suggests patterns of communication within families influence the ways in which they engage loved ones who may be misusing substances like prescription opioids. However, little is known regarding how strategic health messages about family communication influence individuals' intentions to engage in conversations about substance misuse. Applying a normative approach, we conducted a (2 × 2) between-participants experiment examining whether messages advocating indirect (versus direct) communication are more effective for individuals (n = 613) who describe their family as having a low (versus high) conversation orientation. Univariate analysis of variance tests show match effects for message attitudes and message elaboration. For intentions to talk with a loved one about the risks of OUD, there was only evidence of a matching effect between the message advocating indirect communication with low conversation audiences. Both message types were equally effective at influencing intentions for high conversation participants. These findings suggest message designers should consider the kinds of communication behaviors and actions advocated in appeals targeting family members. Messages that are inclusive of the conversation dynamics of particular audiences may have greater effect. In particular, for low conversation audiences, messages advocating an indirect approach may be more effective at motivating intentions to engage someone who is misusing opioids.

6.
J Cell Mol Med ; 25(6): 2885-2899, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534963

RESUMO

Inflammation is a biological process that exists in a large number of diseases. If the magnitude or duration of inflammation becomes uncontrolled, inflammation may cause pathological damage to the host. HMGB1 and NF-κB have been shown to play pivotal roles in inflammation-related diseases. New drugs aimed at inhibiting HMGB1 expression have become a key research focus. In the present study, we showed that paeonol (Pae), the main active component of Paeonia suffruticosa, decreases the expression of inflammatory cytokines and inhibits the translocation of HMGB1 induced by lipopolysaccharide (LPS). By constructing HMGB1-overexpressing (HMGB1+ ) and HMGB1-mutant (HMGB1m ) RAW264.7 cells, we found that the nuclear HMGB1 could induce an LPS-tolerant state in RAW264.7 cells and that paeonol had no influence on the expression of inflammatory cytokines in HMGB1m RAW264.7 cells. In addition, the anti-inflammatory property of paeonol was lost in HMGB1 conditional knockout mice, indicating that HMGB1 is a target of paeonol and a mediator through which paeonol exerts its anti-inflammatory function. Additionally, we also found that HMGB1 and P50 competitively bound with P65, thus inactivating the NF-κB pathway. Our research confirmed the anti-inflammation property of paeonol and suggests that inhibiting the translocation of HMGB1 could be a new strategy for treating inflammation.


Assuntos
Acetofenonas/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Proteína HMGB1/metabolismo , Acetofenonas/química , Animais , Anti-Inflamatórios/química , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Proteína HMGB1/química , Proteína HMGB1/genética , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Knockout , Modelos Moleculares , NF-kappa B/metabolismo , Transporte Proteico , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
7.
Microb Pathog ; 154: 104865, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33771628

RESUMO

Streptococcus suis (S.suis)is an important zoonotic pathogen in pigs and human. Bacterial ghosts (BGs) which are empty envelopes were used recently as efficient delivery system in vaccine development. In this study, S.suis ghosts were prepared and protective efficacy was evaluated in mice. Sodium hydroxide was used to prepare S.suis ghosts which were visualized under scanning electron microscopy. The optimum concentration of is Sodium hydroxide 6 mg/mL for ghosts formed. To investigate the S.suis ghosts as a candidate vaccine, the 50 BALB/c mice were randomly divided into three groups: Group A (control group), group B (subcutaneous injection of inactivated S.suis 2), group C (subcutaneous injection of inactivated S.suis 9), group D (subcutaneous injection of S.suis 2 ghosts), group E (subcutaneous injection of S.suis 9 ghosts). Serum were collected from five groups on the day of 7, 14, 21 and 28 after the first immunization for potency assay. Indirect ELISA results showed that antibody titer of blood serum of mice from group S.suis2 ghosts and group S.suis9 ghosts were significantly higher than blank group(P < 0.01), but were approximate to the conventional inactivated vaccine group SS2. In comparison with the conventional inactivated vaccine, S.suis ghosts as candidate vaccine strategy showed the excellent immunogenicity and provided protection against S.suis challenge in mice model.


Assuntos
Infecções Estreptocócicas , Streptococcus suis , Doenças dos Suínos , Animais , Anticorpos Antibacterianos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estreptocócicas/prevenção & controle , Suínos , Vacinas de Produtos Inativados
8.
J Dairy Sci ; 104(4): 4893-4903, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33551160

RESUMO

Streptococcus agalactiae is a contagious pathogen that causes bovine mastitis worldwide, resulting in considerable economic losses. In this study, we isolated 42 S. agalactiae strains in 379 milk samples from cows with subclinical mastitis on 15 dairy farms in 12 Chinese provinces. Analysis based on capsular typing and multilocus sequence typing, combined with patterns of virulence gene scanning and antimicrobial resistance, identified the lineages and populations of the isolates. We grouped the 42 isolates into 7 sequence types belonging to 6 clonal complexes, mainly CC103 (31/42 isolates; 73.8%). We identified an ST-23 strain named Sa 129 for the first time on Chinese dairy farms-this strain is usually associated with human isolates. Capsular types Ia and II were predominant in capsular typing. The prevalence of virulence profile 1 (bibA, cfb, cspA, cylE, fbsA, fbsB, hylB, and pavA) was 64.3%, and represented the main trend in China. With respect to antimicrobial resistance, most isolates were susceptible to ß-lactams, rifamycin, glycopeptides, and oxazolidone; resistance to several antimicrobial agents, including lincomycin, clindamycin, and doxycycline, varied in 4 different regions. Our research provides a profile for the molecular epidemiology, multilocus sequence typing, antimicrobial resistance, and virulence gene clustering of S. agalactiae, and may be beneficial for the clinical monitoring, prevention, and control of mastitis in dairy cattle.


Assuntos
Doenças dos Bovinos , Mastite Bovina , Mastite , Animais , Antibacterianos/farmacologia , Bovinos , China/epidemiologia , Análise por Conglomerados , Feminino , Mastite/veterinária , Mastite Bovina/epidemiologia , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Streptococcus agalactiae/genética , Virulência/genética , Fatores de Virulência/genética
9.
Int J Mol Sci ; 22(24)2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34947996

RESUMO

Cellulose synthesis is a complex process in plant cells that is important for wood processing, pulping, and papermaking. Cellulose synthesis begins with the glycosylation of sitosterol by sitosterol glycosyltransferase (SGT) to produce sitosterol-glucoside (SG), which acts as the guiding primer for cellulose production. However, the biological functions of SGTs in Populus tomentosa(P. tomentosa) remain largely unknown. Two full-length PtSGT genes (PtSGT1 and PtSGT4) were previously isolated from P. tomentosa and characterized. In the present study, CRISPR/Cas9 gene-editing technology was used to construct PtSGT1-sgRNA and PtSGT4-sgRNA expression vectors, which were genetically transformed into P. tomentosa using the Agrobacterium-mediated method to obtain transgenic lines. Nucleic acid and amino acid sequencing analysis revealed both base insertions and deletions, in addition to reading frame shifts and early termination of translation in the transgenic lines. Sugar metabolism analysis indicated that sucrose and fructose were significantly downregulated in stems and leaves of mutant PtSGT1-1 and PtSGT4-1. Glucose levels did not change significantly in roots and stems of PtSGT1-1 mutants; however, glucose was significantly upregulated in stems and downregulated in leaves of the PtSGT4-1 mutants. Dissection of the plants revealed disordered and loosely arranged xylem cells in the PtSGT4-1 mutant, which were larger and thinner than those of the wild-type. This work will enhance our understanding of cellulose synthesis in the cell walls of woody plants.


Assuntos
Celulose/biossíntese , Clonagem Molecular/métodos , Glucosiltransferases/genética , Populus/metabolismo , Agrobacterium/genética , Sistemas CRISPR-Cas , Regulação da Expressão Gênica de Plantas , Glucose/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Caules de Planta/genética , Caules de Planta/metabolismo , Populus/genética , Sacarose/metabolismo , Transformação Bacteriana , Madeira/genética
10.
Microsc Microanal ; 25(1): 250-256, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30712524

RESUMO

Little is known of the olfactory mechanisms of host detection in the ovipositors of endoparasitoids and ectoparasitoids. An endoparasitoid Aprostocetus causalis La Salle & Wu (Hymenoptera: Eulophidae) and an ectoparasitoid Quadrastichus mendeli Kim & La Salle (Hymenoptera: Eulophidae: Tetrastichinae) are the two parasitoids of the eucalyptus gall wasp Leptocybe spp. Structures and sense organs of ovipositors of A. causalis and Q. mendeli were studied using scanning and transmission electron microscopy, which provided essential information for exploring the mechanism of host detection by endoparasitoid and ectoparasitoid. The ovipositors of two parasitoids consisted of the first and second valvulae and ended in a pointed tip. There were three types of microtrichia, two types of sensilla chaetica, and one type of sensilla campaniformia on the ovipositors of A. causalis and Q. mendeli. However, Q. mendeli has the fourth type of microtrichia on the ovipositor. The morphology, types, distribution, length, and width of these sensilla and microtrichia were described, and their possible functions are discussed in conjunction with the stinging, oviposition, and the host selection process.


Assuntos
Himenópteros/ultraestrutura , Oviposição , Órgãos dos Sentidos/ultraestrutura , Vespas/anatomia & histologia , Animais , China , Eucalyptus/parasitologia , Feminino , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Sensilas/ultraestrutura
12.
Eur J Pharmacol ; 973: 176574, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642670

RESUMO

Osteoporosis is a multifaceted skeletal disorder characterized by reduced bone mass and structural deterioration, posing a significant public health challenge, particularly in the elderly population. Treatment strategies for osteoporosis primarily focus on inhibiting bone resorption and promoting bone formation. However, the effectiveness and limitations of current therapeutic approaches underscore the need for innovative methods. This review explores emerging molecular targets within crucial signaling pathways, including wingless/integrated (WNT), bone morphogenetic protein (BMP), hedgehog (HH), and Notch signaling pathway, to understand their roles in osteogenesis regulation. The identification of crosstalk targets between these pathways further enhances our comprehension of the intricate bone metabolism cycle. In summary, unraveling the molecular complexity of osteoporosis provides insights into potential therapeutic targets beyond conventional methods, offering a promising avenue for the development of new anabolic drugs.


Assuntos
Osteogênese , Osteoporose , Transdução de Sinais , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Animais , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Hedgehog/metabolismo , Terapia de Alvo Molecular , Receptores Notch/metabolismo
13.
J Cancer ; 15(14): 4623-4635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006089

RESUMO

Background: Breast cancer is the second most common cause of cancer-related mortality globally. Apolipoprotein L3 (APOL3), a member of the apolipoprotein family, has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, the functions and underlying mechanisms of APOL3 in breast cancer have yet to be elucidated. Methods: The patient data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) assays were used to assess expression of APOL3. Cell proliferation rates were determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used to examine cell cycle distribution. Western blotting was conducted to investigate the expression of cell cycle related proteins. A xenograft model was used to evaluate the effect of APOL3 in vivo. APOL3-binding proteins were identified through mass spectrometry, co-immunoprecipitation (CO-IP) assay and immunofluorescence assay. Results: APOL3 expression was significantly downregulated in breast cancer, and its low expression was correlated with poor prognostic outcomes. Overexpression of APOL3 suppressed breast cancer cell proliferation, induced cell cycle disruption. Conversely, knockdown of APOL3 promoted cell proliferation. In vivo animal experiments demonstrated that APOL3 overexpression can inhibit tumor proliferation. Mass spectrometry, CO-IP and immunofluorescence assay confirmed the interaction between APOL3 and Y-box binding protein 1 (YBX1). Furthermore, YBX1 knockdown following APOL3 knockdown mitigated the enhanced proliferation. These results provide new ideas for clinically targeting APOL3 to inhibit proliferation in breast cancer. Conclusions: Our findings indicate that APOL3 inhibits breast cancer cell proliferation and cell cycle modulating P53 pathway through the interaction of YBX1.

14.
J Cataract Refract Surg ; 50(3): 283-288, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085243

RESUMO

PURPOSE: To compare the effect of capsular bend on the rotational stability between 2 toric intraocular lenses (IOLs). SETTING: Eye Hospital of Wenzhou Medical University, Hangzhou, Zhejiang Province, China. DESIGN: Prospective study. METHODS: Patients with preexisting astigmatism received AcrySof IQ (SN6AT) or TECNIS (ZCT/ZMT) toric IOL during cataract surgery. CASIA2 was used to record the toric IOL axial orientation and capsular bend index (CBI) at the 1-day, 1-week, 1-month, and 3-month interval postoperatively. The postoperative rotational stability and CBI of both models were compared. RESULTS: A total of 58 eyes from 58 patients were enrolled in this study. The total misalignment of the TECNIS (ZCT/ZMT) group (6.96 ± 5.10 degrees, 7.41 ± 5.19 degrees, 6.93 ± 5.29 degrees, and 6.86 ± 5. 27 degrees) was significantly higher than that of the AcrySof IQ (SN6AT) group (3.55 ± 2.21 degrees, 4.00 ± 2.74 degrees, 3.72 ± 2.72 degrees, and 3.52 ± 2.50 degrees) at all follow-up intervals ( P < .05). The mean rotation of the TECNIS (ZCT/ZMT) group (2.66 ± 2.18 degrees) was significantly greater than that of the AcrySof IQ (SN6AT) group (1.65 ± 1.47 degrees) from 1 day to 1 week postoperatively ( P < .05). The capsular bend formation in the TECNIS (ZCT/ZMT) group was delayed compared with the AcrySof IQ (SN6AT) group ( P < .05, at the 1-week, 1-month, and 3-month interval). The TECNIS (ZCT/ZMT) group showed fibrosis in the peripheral anterior capsule, leading to its stretching away from the IOL surface, while the AcrySof IQ (SN6AT) group exhibited gentle adherence of the anterior capsule to the IOL surface. CONCLUSIONS: The AcrySof IQ toric IOL (SN6AT) exhibited greater rotational stability than the TECNIS toric IOL (ZCT/ZMT), which may partially result from the delay in capsular bend formation of TECNIS at the 1-day to 1-week follow-up postoperatively.


Assuntos
Astigmatismo , Lentes Intraoculares , Facoemulsificação , Humanos , Refração Ocular , Implante de Lente Intraocular , Acuidade Visual , Estudos Prospectivos , Desenho de Prótese , Astigmatismo/cirurgia
15.
J Ethnopharmacol ; 325: 117861, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38316223

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has made enormous strides recently in the discovery of anti-herpes simplex virus (HSV) drugs under the guidance of TCM theory. Longdan Xiegan Decoction (LXD), a formulation recorded in the Pharmacopoeia of the People's Republic of China, has proved to be effective against HSV infection. However, its effective components and action mechanism remain unclear. AIM OF THE STUDY: To investigate the effective components and mechanisms of LXD in treating HSV infection based on network pharmacology and experimental validation. MATERIALS AND METHODS: The anti-HSV activities of key compounds predicted by network analysis were detected by antiviral tests. High-performance liquid chromatography (HPLC) was applied to identify the main components of the LXD aqueous extract. Time-of-addition assay and infectivity inhibition reversibility assay were conducted to identify the potential antiviral mechanisms of licochalcone B (LCB). Additionally, we assessed the antiviral effect of LCB in vivo by use of body weight, viral load, histological analysis, and scoring of genital lesions in an HSV2-infected mouse model. RESULTS: Our data demonstrated that some components exhibited significant anti-HSV1/2 activity in vitro, including quercetin, kaempferol, wogonin, formononetin, naringenin, baicalein, isorhamnetin, glabridin, licochalcone A, echinatin, oroxylin A, isoliquiritigenin, pinocembrin, LCB and acacetin. HPLC analysis showed that LCB was the main component of LXD aqueous extract. In vitro experiments revealed that LCB not only inactivated HSV2 particles, but also inhibited HSV2 multiplication through the inhibition of the phosphorylation of Akt and its downstream targets. In vivo experiments confirmed that LCB could significantly reduce viral titer, delay weight loss, and alleviate pathological changes in vaginal tissue in vaginal infection mouse models. CONCLUSION: LCB acted as the main component of LXD, with significant anti-HSV2 infection effects both in vivo and in vitro. This study provides additional evidence of the healing efficacy of LXD against HSV infection and presents an efficient analytical method for further investigation of the mechanisms of TCM in prevention and treatment of various diseases.


Assuntos
Chalconas , Medicamentos de Ervas Chinesas , Herpes Simples , Feminino , Animais , Camundongos , Humanos , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Herpes Simples/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Simulação de Acoplamento Molecular
16.
Biomed Pharmacother ; 170: 116018, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113628

RESUMO

Hepatocellular carcinoma (HCC) is one of the most fatal solid malignancies worldwide. Evidence suggests that thrombin stimulates tumor progression via fibrin formation and platelet activation. Meanwhile, we also found a correlation between thrombin and HCC through bioinformatics analysis. Dabigatran is a selective, direct thrombin inhibitor that reversibly binds to thrombin. Dabigatran was used as the lead agent in this study, and 19 dabigatran derivatives were designed and synthesized based on docking mode. The thrombin-inhibitory activity of the derivative AX-2 was slightly better than that of dabigatran. BX-2, a prodrug of AX-2, showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and effectively antagonized proliferation of HCC tumor cells induced by thrombin at the cellular level. Furthermore, BX-2 reduced tumor volume, weight, lung metastasis, and secondary tumor occurrence in nude mouse models. BX-2 combined with sorafenib increased sorafenib efficacy. This study lays the foundation for discovering new anti-HCC mechanism based on thrombin. BX-2 can be used as an anti-HCC drug lead for further research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Trombina/metabolismo , Sorafenibe/farmacologia , Neoplasias Hepáticas/tratamento farmacológico
17.
bioRxiv ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38979300

RESUMO

The ability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to infect a wide-range of species raises significant concerns regarding both human-to-animal and animal-to-human transmission. There is an increasing demand for highly sensitive, rapid, and simple diagnostic assays that can detect viral infection across various species. In this study, we developed a biosensor assay that adapted a monoclonal-antibody (mAb)-based blocking ELISA format into an Activate Capture + Digital Counting (AC + DC)-based immunoassay. The assay employs a photonic crystal (PC) biosensor, gold-nanoparticle (AuNP) tags, SARS-CoV-2 nucleocapsid (N) protein, and specific anti-N mAb to detect antibody responses in animals exposed with SARS-CoV-2. We demonstrated a simple 2-step 15-min test that was capable of detecting as low as 12.5 ng of antibody in controlled standard serum samples. Based on an evaluation of 176 cat serum samples with known antibody status, an optimal percentage of inhibition (PI) cut-off value of 0.588 resulted in a diagnostic sensitivity of 98.3% and a diagnostic specificity of 96.5%. The test is highly repeatable with low variation coefficients of 2.04%, 2.73%, and 4.87% across different runs, within a single run, and on a single chip, respectively. The test was further employed to detect antibody responses in multiple animal species as well as investigate dynamics of antibody response in experimentally infected cats. This test platform provides an important tool for rapid field surveillance of SARS-CoV-2 infection across multiple species.

18.
Front Immunol ; 15: 1371379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881888

RESUMO

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , DNA Helicases , Fatores de Transcrição , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , DNA Helicases/genética , DNA Helicases/deficiência , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Transcrição/genética , Proteínas Nucleares/genética , Proteínas Nucleares/deficiência , Etoposídeo/uso terapêutico , Etoposídeo/administração & dosagem , Masculino , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Resultado do Tratamento , Feminino
19.
Artigo em Inglês | MEDLINE | ID: mdl-38751471

RESUMO

Background and Objective: Breast cancer gene expression signatures are developing rapidly and are expected to better understand the intrinsic features of the tumor, and also to optimize the treatment strategy in clinical practice. This review is to summarize the controversy and consensus in clinical practice of gene expression signatures, and to provide our perspective on these issues as well as recommendation for future direction. Methods: We reviewed English publications in PubMed related to breast cancer gene expression signatures from 2002 to 2022. Key Content and Findings: Five mature commercial gene expression signatures: Oncotype, MammaPrint, Prosigna/PAM50, EndoPredict and Breast Cancer Index (BCI) are available to provide the prognostic and predictive assessment. Although they could help to evaluate the risk of recurrence and to predict the benefits of certain treatments, their applications remain challenging. Treatment decisions should be determined by a combination of related clinical pathological factors in clinical practice. Conclusions: Gene expression signatures could assist in the determination of the adjuvant therapy of early-stage breast cancer. The prospective randomized clinical trials showed that chemotherapy may be exempted in low-risk patients. More sufficient data are expected for the application in radiotherapy, extended endocrine therapy, and neoadjuvant treatment. The treatment cannot be determined by a single factor but by comprehensive assessments of clinicopathological factors, test purpose, and cost-effectiveness. Patients will benefit from personalized treatments with the publication of further evidence.

20.
Retin Cases Brief Rep ; 17(4): 406-409, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37364200

RESUMO

BACKGROUND/PURPOSE: To report a case of uveal effusion associated with localized scleroderma because of scleral collagen fibrosis. Partial-thickness sclerectomy treatment was successful in acquiring the resolution of the uveal effusion. METHODS: Case report. RESULTS: A 44-year-old Chinese woman with known localized scleroderma visited the retinal clinic complaining of insidious onset blurring of vision in both eyes for 8 months. The best-corrected visual acuity was 20/200. Ophthalmoscopy revealed apparent inferior bullous serous retinal detachments in the right eye. Optical coherence tomography showed subretinal fluid and folds of the retinal pigment epithelium layer in both eyes. B-scan ultrasonographic image of the right eye confirmed a 360-degree serous retinal detachment in the right eye accompanied with increased thickness of the ocular wall. Ultrasound biomicroscopy of the anterior segment detected a shallow ciliary body detachment in the right eye. Fluorescein angiography and indocyanine green angiography demonstrated the leopard-spot pattern in all phases. Partial-thickness sclerectomy treatment was successful in acquiring the resolution of the uveal effusion. Histopathologic examinations of the sclera flaps revealed scleral collagen fibrosis. CONCLUSION: This clinicopathologic report first describes a patient with localized scleroderma and scleral collagen fibrosis, resulting in uveal effusion that responded to partial-thickness sclerectomy.


Assuntos
Descolamento Retiniano , Esclerodermia Localizada , Doenças da Úvea , Feminino , Humanos , Adulto , Esclera/cirurgia , Doenças da Úvea/diagnóstico , Doenças da Úvea/cirurgia , Esclerodermia Localizada/complicações , Esclerodermia Localizada/diagnóstico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/patologia , Tomografia de Coerência Óptica , Angiofluoresceinografia , Colágeno
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