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1.
BMC Genomics ; 25(1): 776, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123103

RESUMO

BACKGROUND: Transcription factors (TFs) of plant-specific SHORT INTERNODES (SHI) family play a significant role in regulating development and metabolism in plants. In Artemisia annua, various TFs from different families have been discovered to regulate the accumulation of artemisinin. However, specific members of the SHI family in A. annua (AaSHIs) have not been identified to regulate the biosynthesis of artemisinin. RESULTS: We found five AaSHI genes (AaSHI1 to AaSHI5) in the A. annua genome. The expression levels of AaSHI1, AaSHI2, AaSHI3 and AaSHI4 genes were higher in trichomes and young leaves, also induced by light and decreased when the plants were subjected to dark treatment. The expression pattern of these four AaSHI genes was consistent with the expression pattern of four structural genes of artemisinin biosynthesis and their specific regulatory factors. Dual-luciferase reporter assays, yeast one-hybrid assays, and transient transformation in A. annua provided the evidence that AaSHI1 could directly bind to the promoters of structural genes AaADS and AaCYP71AV1, and positively regulate their expressions. This study has presented candidate genes, with AaSHI1 in particular, that can be considered for the metabolic engineering of artemisinin biosynthesis in A. annua. CONCLUSIONS: Overall, a genome-wide analysis of the AaSHI TF family of A. annua was conducted. Five AaSHIs were identified in A. annua genome. Among the identified AaSHIs, AaSHI1 was found to be localized to the nucleus and activate the expression of structural genes of artemisinin biosynthesis including AaADS and AaCYP71AV1. These results indicated that AaSHI1 had positive roles in modulating artemisinin biosynthesis, providing candidate genes for obtaining high-quality new A. annua germplasms.


Assuntos
Artemisia annua , Artemisininas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Artemisia annua/genética , Artemisia annua/metabolismo , Artemisininas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Filogenia
2.
Clin Immunol ; 258: 109861, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065370

RESUMO

With increasing stress in daily life and work, subhealth conditions induced by "Shi-Re Shanghuo" syndrome was gradually universal. "Huanglian Jiedu Wan" (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of "Shi-Re Shanghuo" with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on "Shi-Re Shanghuo" syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene "Shi-Re Shanghuo" syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by "Shi-Re Shang Huo" was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of "Shi-Re Shanghuo" syndrome treated with HLJDW.


Assuntos
Medicamentos de Ervas Chinesas , Metaloproteinase 9 da Matriz , Animais , Ácido Araquidônico , Biomarcadores , Simulação de Acoplamento Molecular , Succinatos/uso terapêutico , Ácido Succínico , Humanos
3.
Pharm Biol ; 62(1): 356-366, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38720666

RESUMO

CONTEXT: Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown. OBJECTIVE: This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota. MATERIALS AND METHODS: 120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics. RESULTS: Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism. DISCUSSION AND CONCLUSION: The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored. TRIAL REGISTRATION: ChiCTR2300076136, retrospectively registered.


Assuntos
Medicamentos de Ervas Chinesas , Disbiose , Microbioma Gastrointestinal , Proteinúria , Insuficiência Renal Crônica , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Feminino , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/tratamento farmacológico , Proteinúria/tratamento farmacológico , Proteinúria/microbiologia , Pessoa de Meia-Idade , Medicamentos de Ervas Chinesas/farmacologia , Fezes/microbiologia , Idoso , Adulto , Medicina Tradicional Chinesa/métodos
4.
Calcif Tissue Int ; 113(6): 630-639, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37980279

RESUMO

Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused mostly by benign tumors that secrete fibroblast growth factor-23. Because of nonspecific symptoms, the diagnostic delay is long, and therapy can be challenging. Moreover, epidemiological data on TIO are scarce owing to its rarity. Therefore, this study aimed to quantify TIO's incidence rates and prevalence in Germany. Retrospective longitudinal and cross-sectional analyses were conducted using anonymized German claims data from the statutory health insurance (SHI) database. This database, which comprises the data of approximately 5 million insurants, is a representative sample of the German population and supports national projections. As there is no unique International Statistical Classification of Diseases and Related Health Problems (ICD) code for TIO, operational categories based on different surrogates were defined to determine the prevalence and incidence rates of TIO among probable patients. This study showed that TIO has a prevalence of (documented code, advanced imaging, medication, or tumor removal) 0.187 per 100,000 persons and an incidence rate of ≤ 0.094 per 100,000 person years. This analysis provides the first epidemiological insight into German patients with TIO. Despite the general limitations associated with the analysis of SHI claims data of ultra-rare diseases, we believe that this analysis provides a sound basis for further analysis, particularly with regard to the care situation of patients with TIO.


Assuntos
Diagnóstico Tardio , Osteomalacia , Humanos , Estudos Retrospectivos , Estudos Transversais , Diagnóstico Tardio/efeitos adversos , Osteomalacia/epidemiologia , Osteomalacia/etiologia , Alemanha/epidemiologia
5.
Can J Neurol Sci ; 50(2): 228-233, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35190003

RESUMO

BACKGROUND: The split-hand index (SHI) (first dorsal interosseous (FDI) × abductor pollicis brevis (APB)/abductor digiti minimi muscle (ADM)) has been suggested as a useful measure for amyotrophic lateral sclerosis (ALS) diagnosis, using electrophysiological and sonographic indices. In the present study, we aimed to explore the specificity of SHI derived by muscle ultrasound (MUS) for the diagnosis of ALS and spinal muscular atrophy (SMA). METHODS: Healthy controls (n = 65) were prospectively recruited at the Prosserman Family Neuromuscular clinic at Toronto General Hospital, from October to December 2018. In addition, 181 patients with ALS (n = 91), SMA (n = 33), polyneuropathy (n = 35), and myopathy (n = 22) were prospectively recruited at the neuromuscular clinic at Tel Aviv Sourasky Medical Center, from December 2018 to December 2020. All subjects underwent quantitative sonographic evaluation of muscle thickness, including the right APB, FDI, and ADM muscles. Area under curve (AUC), sensitivity, and specificity were determined for differentiating between groups. RESULTS: Although SHI showed good to excellent accuracy for differentiating each patient subgroup from controls (AUC 0.83-0.92), poorer diagnostic accuracy was shown for differentiating between different patient subgroups (AUC 0.54-0.74). CONCLUSIONS: Sonographic SHI is useful for differentiating patients from healthy controls, but might be not specific for motor neuron disease.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Sensibilidade e Especificidade , Ultrassonografia
6.
Exp Parasitol ; 246: 108451, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36584786

RESUMO

"Shi Ying Zi" powder is a traditional Chinese herbal formula for preventing and treating coccidiosis. In our previous studies, it showed anticoccidial effects and exhibited the potential to control Eimeria tenella infection. In this research, we evaluated the antioxidation and immune effect of "Shi Ying Zi" powder and its effective active ingredient osthole on coccidiosis-infected broilers to explore the mechanism of its anticoccidial effect. We analyzed changes in the antioxidant index, the pathological changes in cecum, immune index of serum and composition of cecal flora. The results showed that the use of "Shi Ying Zi" powder and osthole alleviated the pathological changes in the cecum, spleen and bursa of Fabricius, upregulated the spleen and bursal weigh index. "Shi Ying Zi" powder of 10 g/kg effectively rocovered the contents of interleukins and immunoglobulin in serum. Osthole increased the proportion of Firmicutes, Actino-bacteria and Lactobacillus in the cecum. In summary, "Shi Ying Zi" powder and osthole have anticoccidial effects, and they also can active the immunity, antioxidant functions and upregulate the beneficial bacteria population in Eimeria tenella-infected broilers.


Assuntos
Coccidiose , Eimeria tenella , Doenças das Aves Domésticas , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Galinhas , Pós , Coccidiose/tratamento farmacológico , Coccidiose/veterinária , Bactérias , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controle , Ceco/patologia
7.
Fish Physiol Biochem ; 49(2): 351-370, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36995511

RESUMO

This study was conducted to investigate the structural and ontogenetic development of the skeletal system and digestive tract histologically and enzymatically in larvae of shi drum (U. cirrosa) under intensive rearing conditions until 40 days after hatching (DAH). Among digestive enzymes, amylase was detected at 0.89 ± 0.12 mU mg protein-1 on the first hatching day. The specific activities of trypsin and lipase were detected simultaneously with mouth opening on 3 DAH with 28.47 ± 3.52 and 2.8 ± 0.32 mU mg protein-1, respectively. In addition, pepsin was found for the first time at 0.88 ± 0.21 mU mg protein-1 on 15 DAH in association with stomach formation and increased sharply up to 40 DAH. In the structural development of the skeletal system, the development of the caudal fin in larvae was morphologically associated with the flexion of the notochord. It was observed that the shape of the fin and spine, which reached 40 DAH, became similar to the adult shape. Histologically, 3 DAH, the mouth and anus were opened. The formation of the primitive stomach was observed at the end of the seventh day-the pyloric sphincter formed between 13 and 18 days. A functional stomach was seen on the 15th DAH. Therefore, U. cirrosa is believed to have critical aquaculture potential that can be cultured under intensive conditions. The developmental profile of skeletal, enzymatic, and histological ontogeny observed in U. cirrosa is similar to that described for other sciaenid species.


Assuntos
Perciformes , Animais , Larva , Trato Gastrointestinal , Lipase , Tripsina
8.
Artigo em Alemão | MEDLINE | ID: mdl-37436444

RESUMO

BACKGROUND: We investigated the impact of HIV pre-exposure prophylaxis (PrEP) as a new service of the statutory health insurance (SHI) on the incidence of HIV and other sexually transmitted infections (STIs) in Germany. In addition, PrEP needs and access barriers were analyzed. METHODS: The following data were evaluated as part of the evaluation project: HIV and syphilis notification data and extended surveillance by the Robert Koch Institute (RKI), pharmacy prescription data, SHI routine data, PrEP use in HIV-specialty care centers, Checkpoint, the BRAHMS and PrApp studies, as well as a community board. RESULTS: The majority of PrEP users were male (98-99%), primarily aged between 25-45 years, and predominantly of German nationality or origin (67-82%). The majority were men who have sex with men (99%). With regard to HIV infections, PrEP proved to be highly effective. There were only isolated cases of HIV infections (HIV incidence rate 0.08/100 person years); in most cases the suspected reason was low adherence. The incidences of chlamydia, gonorrhea, and syphilis did not increase but remained almost the same or even decreased. A need for information on PrEP for people in trans*/non-binary communities, sex workers, migrants, and drug users emerged. Needs-based services for target groups at increased risk of HIV are necessary. DISCUSSION: PrEP proved to be a very effective HIV prevention method. The partly feared indirect negative influences on STI rates were not confirmed in this study. Due to the temporal overlap with the containment measures during the COVID-19 pandemic, a longer observation period would be desirable for a conclusive assessment.


Assuntos
COVID-19 , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Profilaxia Pré-Exposição/métodos , Homossexualidade Masculina , Sífilis/epidemiologia , Sífilis/prevenção & controle , Pandemias/prevenção & controle , Alemanha/epidemiologia , COVID-19/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Seguro Saúde
9.
N C Med J ; 85(1): 64-69, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39374351

RESUMO

Background: COVID-19 has amplified the health and economic disparities in Native American communities. However, there are limited data from Native American populations. This study is the first phase of the Building Resilience And Vital Equity (BRAVE) project, the scope of which is to understand Indigenous perceptions, attitudes, and behaviors about COVID-19 and design and implement culturally sensitive interventions to increase testing and vaccinations among Native American communities. Method: We recruited 26 Native Americans and conducted open-ended, semi-structured interviews to explore participants' perceptions of COVID-19 and related themes, such as needed support, informational sources, trust, communication, and protection of elders. Results: The results show that wearing a mask, hand sanitizing, and social distancing had very high support while perceptions of testing and vaccination decisions were mixed. Additionally, two themes stand out: the lack of reliable information resources to learn about COVID-19 and the lack of trust in the government. Limitation: This study included a small sample size, which makes it difficult to include participants from diverse demographic backgrounds. Lack of familiarity with the online meeting format and the limited internet access in some indigenous communities may have prevented some people from participating. Conclusion: The findings confirmed the need to improve existing public health information infrastructure and helped explain the intensified impact of COVID-19 on the Indigenous marginalized community. The findings help identify the key factors that affect Native Americans' testing and vaccination decisions and provide guidance on the designs of community intervention programs.


Assuntos
COVID-19 , Indígenas Norte-Americanos , Pesquisa Qualitativa , Humanos , COVID-19/prevenção & controle , COVID-19/etnologia , North Carolina , Indígenas Norte-Americanos/psicologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em Saúde , SARS-CoV-2 , Confiança , Idoso , Entrevistas como Assunto , Adulto Jovem
10.
Biomed Chromatogr ; 36(5): e5324, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34993982

RESUMO

Da-Huang-Xiao-Shi decoction (DHXSD) is a traditional Chinese medicine formula and is used to treat cholestasis. In this study, we developed a reliable and comprehensive HPLC coupled with a linear ion trap-Orbitrap mass spectrometry method for the separation and determination of 21 components including six alkaloids, five anthraquinones, three tannins, three terpenes, two iridoid glycosides, one organic acid and one flavonoid in DHXSD. A C18 column was eluted using a gradient mobile phase at a flow rate of 1 ml/min. Detection was operated with an electrospray ionization source in positive and negative ion modes using selective ion monitoring. The calibration curves for all analytes showed good linearity (r > 0.9901), and the inter- and intra-day precision did not exceed 4.98%. The recovery, repeatability and stability were also within the acceptable limits. The method was successfully applied to determine multiple active constituents in DHXSD and its constituent herbs. Compared with Da Huang, the total contents of the five anthraquinones were significantly higher in DHXSD. However, the changes in the components from Zhi Zi/Huang Bo were complicated in DHXSD. The study could serve as a fundamental reference for establishing comprehensive DHXSD quality control measures and be helpful to understand some compatibility laws of DHXSD.


Assuntos
Medicamentos de Ervas Chinesas , Antraquinonas/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos
11.
J Integr Neurosci ; 21(6): 164, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36424738

RESUMO

BACKGROUND: Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. METHODS: Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. RESULTS: Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. CONCLUSIONS: Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.


Assuntos
Clozapina , Disfunção Cognitiva , Esquizofrenia , Ratos , Animais , Maleato de Dizocilpina/efeitos adversos , Esquizofrenia/induzido quimicamente , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Clozapina/efeitos adversos , Modelos Animais de Doenças , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico
12.
Arch Gynecol Obstet ; 306(2): 513-521, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35253085

RESUMO

PURPOSE: The transition from the fertile phase of life to menopause is associated with numerous physical changes. Hormone replacement therapy (HRT), as the most effective and efficient form of drug treatment, involves the use of oestrogens and progestins with the aim of increasing health-related quality of life through symptom reduction, sleep improvement and affect enhancement. METHODS: The medical care situation and disease burden of menopausal women was investigated by means of a survey of 1000 women aged 45-60 years on the topics of quality of life, menopause and HRT and a quantitative, longitudinal healthcare study based on an anonymised and age- and sex-adjusted Statutory Health Insurance (SHI) routine data set with approximately four million anonymous insured persons per year. RESULTS: Out of more than half a million women aged 35-70 years, and with statutory health insurance, (n = 613,104), 14% (n = 82,785) had climacteric disorder documented as a first diagnosis in 2014. The proportion of women with the climacteric disorder, who were prescribed HRT on an outpatient basis, was 21%; according to the forsa survey, 50% of the women surveyed felt moderate to poorly/very poorly informed about treatment options. CONCLUSION: Findings from the health insurance research conducted with different data sources (survey and SHI claims data) indicate the need for increasing awareness and providing an early and informative education on HRT and its risks and benefits.


Assuntos
Terapia de Reposição de Estrogênios , Qualidade de Vida , Feminino , Alemanha , Pesquisa sobre Serviços de Saúde , Humanos , Menopausa , Inquéritos e Questionários
13.
Cas Lek Cesk ; 161(3-4): 159-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36100457

RESUMO

The Islamic Republic of Iran is a very progressive state in the field of medical research and its application. Although the country is fully subject to Islamic law (shari'a) and the influence of Shi'ite clerics, the development of medical science is not limited at all; Shi'ite medical ethics (unlike Sunnite) allows most of the modern medical techniques. Due to this attitude, Iran specializes today in many techniques that are prohibited in other countries for religious or ethical reasons. For example, Iranian research on cloning, cell and gene therapy reaches the world level, patients can use a third-party donor program and surrogacy for infertility treatment, the sale of kidney for transplantation was legalized, gender reassignment surgery is performed, and the country is a centre of cosmetic surgery. All of these services (excluding transplantation) are also offered to foreign patients. Thanks to these unlimited possibilities, high quality and low price, Iran has been currently gaining a strong position in the medical tourism market, not only in the Middle East region, but also worldwide.


Assuntos
Turismo Médico , Ética Médica , Humanos , Irã (Geográfico) , Islamismo , Doadores de Tecidos
14.
Plant J ; 101(1): 87-100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483536

RESUMO

Auxin signaling mediated by various auxin/indole-3-acetic acid (Aux/IAAs) and AUXIN RESPONSE FACTORs (ARFs) regulate lateral root (LR) development by controlling the expression of downstream genes. LATERAL ROOT PRIMORDIUM1 (LRP1), a member of the SHORT INTERNODES/STYLISH (SHI/STY) family, was identified as an auxin-inducible gene. The precise developmental role and molecular regulation of LRP1 in root development remain to be understood. Here we show that LRP1 is expressed in all stages of LR development, besides the primary root. The expression of LRP1 is regulated by histone deacetylation in an auxin-dependent manner. Our genetic interaction studies showed that LRP1 acts downstream of auxin responsive Aux/IAAs-ARFs modules during LR development. We showed that auxin-mediated induction of LRP1 is lost in emerging LRs of slr-1 and arf7arf19 mutants roots. NPA treatment studies showed that LRP1 acts after LR founder cell specification and asymmetric division during LR development. Overexpression of LRP1 (LRP1 OE) showed an increased number of LR primordia (LRP) at stages I, IV and V, resulting in reduced emerged LR density, which suggests that it is involved in LRP development. Interestingly, LRP1-induced expression of YUC4, which is involved in auxin biosynthesis, contributes to the increased accumulation of endogenous auxin in LRP1 OE roots. LRP1 interacts with SHI, STY1, SRS3, SRS6 and SRS7 proteins of the SHI/STY family, indicating their possible redundant role during root development. Our results suggested that auxin and histone deacetylation affect LRP1 expression and it acts downstream of LR forming auxin response modules to negatively regulate LRP development by modulating auxin homeostasis in Arabidopsis thaliana.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Epigênese Genética/genética , Epigênese Genética/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Mutação/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
15.
Exp Eye Res ; 213: 108823, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34752817

RESUMO

Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Naftoquinonas/uso terapêutico , Piruvato Quinase/antagonistas & inibidores , Indutores da Angiogênese/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Western Blotting , Células Cultivadas , Neovascularização de Coroide/enzimologia , Cromatografia Líquida de Alta Pressão , Corantes/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Angiofluoresceinografia , Humanos , Marcação In Situ das Extremidades Cortadas , Verde de Indocianina/administração & dosagem , Macrófagos/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Piruvato Quinase/metabolismo , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo
16.
Chem Pharm Bull (Tokyo) ; 69(10): 1010-1016, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34305073

RESUMO

α,ß-Unsaturated oximes underwent electrophilic epoxidation with in-situ-generated dimethyldioxirane to give the corresponding epoxides in good yields. This reaction is an example of "carbonyl umpolung" by transformation of α,ß-unsaturated ketones to their oximes. Nucleophilic ring-opening reactions of the epoxides afforded α-substituted products. Shi asymmetric epoxidation of the oximes proceeded with moderate enantioselectivity.


Assuntos
Compostos de Epóxi/síntese química , Oximas/química , Compostos de Epóxi/química , Estrutura Molecular
17.
J Asian Nat Prod Res ; 23(8): 764-771, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32602352

RESUMO

Three compounds with diuretic potential were identified from the 95% ethanol extract of Pyrrosia petiolosa (Christ) Ching. Among them, one was a new benzanilide named petiolide A (1), and the other two were phenolic derivatives barbatic acid (2) and kaempferol (3). Their structures were elucidated based on extensive spectral analyses and comparison with the literature data. The docking experiments of all compounds into the active site of the With-No-Lysine kinase 1 (WNK1) domain demonstrated that kaempferol (3) was the most effective component with diuretic potential for its comparative diuretic effect to that of an orally bioavailable WNK inhibitor WNK463 (docking score -10.99 vs -11.09).[Formula: see text].


Assuntos
Diuréticos , Polypodiaceae , Diuréticos/farmacologia , Estrutura Molecular , Extratos Vegetais
18.
Int Orthop ; 45(12): 3233-3242, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34546389

RESUMO

PURPOSE: The purpose of this study is to assess the role of the lateral wall in post-operative clinical outcomes in patients with intertrochanteric fractures treated with the proximal femoral nail anti-rotation-Asia (PFNA-II). METHODS: A cohort of 466 patients (OTA type 31A1 or A2) was divided into two groups: one was intact lateral wall group, and the other was fractured lateral wall group. Radiographic outcomes were measured by using the loss of neck-shaft angle (NSA), femoral neck shortening (FNS), and offset shortening (OS). Functional outcomes were assessed by using the Harris score and SF-36 Physical Component Summary (SF-36 PCS). Post-operative complications were recorded. RESULTS: The fractured lateral wall group had a greater loss of NSA (mean [SD], fractured group (8.7°) [2.7°] vs intact group (4.8°) [2.8°]; mean difference, 3.3° [95% CI 2.9 to 3.8]; P < 0.001) compared with the intact lateral wall group. Similar results were found for FNS and OS. The fractured lateral wall group had a worse Harris scores at the three month follow-up (mean [SD] score, fractured group (66.6) [5.2] points vs intact group (71.3) [5.8] points; mean difference, - 3.3 points [95% CI - 3.9 to - 2.7]; P < 0.001) compared with the intact lateral wall group. Similar results were observed for Harris scores at the three and 12-month follow-ups and SF-36 PCS at the three, six and 12-month follow-ups. The fractured lateral wall group had a higher risk of post-operative complications compared with the intact lateral wall group. CONCLUSION: Among older patients with intertrochanteric fractures, the fractured lateral wall was associated with worse clinical outcomes compared with the intact lateral wall. Clinicians should pay attention to the lateral wall integrity in patients with intertrochanteric fractures treated with the PFNA-II.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Ásia , Pinos Ortopédicos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
19.
J Relig Health ; 60(3): 1952-1968, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32100167

RESUMO

This article explores expressions in how the local Shi'as Muslim women refugees define and interpret their religious identity and gender citizenship in post-authoritarian Indonesia. This article discusses the cases of Shias women from the Sampang Regency, East Java, Indonesia, in the aftermath of the 2012 conflict that made them internally displaced persons (IDPs, Indonesian: pengungsi). This study argues that religious identity and gender citizenship are constructed by these displaced Shias women concerning their belief as to what is considered 'true' in Islam, acquired from the 'Islamic traditions' of their local Islamic teacher (s). Their loyalty to a religious belief does not arise from any independent search for the 'true Islam' but rather from the doctrine of the teachers/spiritual leaders. Enforced loyalty to Shi'as in their everyday communal ritual practices has influenced the formation of these displaced women's religious identity as Shi'ias.


Assuntos
Identidade de Gênero , Islamismo , Feminino , Humanos , Indonésia
20.
J Exp Bot ; 71(4): 1598-1613, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745559

RESUMO

Gene regulation is central for growth, development, and adaptation to environmental changes in all living organisms. Many genes are induced by environmental cues, and the expression of these inducible genes is often repressed under normal conditions. Here, we show that the SHINY2 (SHI2) gene is important for repressing salt-inducible genes and also plays a role in cold response. The shi2 mutant displayed hypersensitivity to cold, abscisic acid (ABA), and LiCl. Map-based cloning demonstrates that SHI2 encodes a DEAD- (Asp-Glu-Ala-Asp) box RNA helicase with similarity to a yeast splicing factor. Transcriptomic analysis of the shi2 mutant in response to cold revealed that the shi2 mutation decreased the number of cold-responsive genes and the magnitude of their response, and resulted in the mis-splicing of some cold-responsive genes. Under salt stress, however, the shi2 mutation increased the number of salt-responsive genes but had a negligible effect on mRNA splicing. Our results suggest that SHI2 is a component in a ready-for-transcription repressor complex important for gene repression under normal conditions, and for gene activation and transcription under stress conditions. In addition, SHI2 also serves as a splicing factor required for proper splicing of cold-responsive genes and affects 5' capping and polyadenylation site selection.


Assuntos
RNA Helicases DEAD-box , Regulação da Expressão Gênica de Plantas , Ácido Abscísico , Aclimatação , Temperatura Baixa , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Splicing de RNA/genética
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