Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 198
Filtrar
1.
Front Pharmacol ; 15: 1363202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560351

RESUMO

Background: Oral mucositis is a major complication for head and neck cancer (HNC) patients after radiotherapy or chemotherapy. A meta-analysis was performed to assess the efficacy of turmeric in the treatment of oral mucositis in HNC patients. Methods: Randomized controlled trials investigating our topic were included in the meta-analysis. The clinical outcomes considered were the severity of oral mucositis, pain level, and weight loss. Results: A total of eight articles that met our inclusion criteria were included in our meta-analysis. At the 3-week follow-up visit, the turmeric group showed significantly lower grades of oral mucositis compared to the control group (p = 0.03). When compared to the placebo group, a significant difference in the degree of oral mucositis was observed at the 4-(p = 0.03) and 6-week (p < 0.00001) follow-up visits. No significant difference in pain levels was observed between the turmeric and control groups at any of the follow-up visits. However, a significant improvement in pain levels for the turmeric group when compared with the placebo group was observed only at the 6-week follow-up visit (p = 0.006). Interestingly, a significant improvement in pain levels was observed for the turmeric group at the 2-, 4-, 5-, and 6-week follow-up visits (p < 0.05) when compared to the non-placebo group. The turmeric group showed less weight loss than the control group at the final follow-up visit (p = 0.03). conclusion: Our meta-analysis showed that using turmeric may be effective in improving both the severity of oral mucositis and pain levels in HNC patients who have received radiotherapy or radiochemotherapy. In addition, the turmeric group experienced less weight loss.

2.
Sensors (Basel) ; 24(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38610405

RESUMO

With the increase in the scale of breeding at modern pastures, the management of dairy cows has become much more challenging, and individual recognition is the key to the implementation of precision farming. Based on the need for low-cost and accurate herd management and for non-stressful and non-invasive individual recognition, we propose a vision-based automatic recognition method for dairy cow ear tags. Firstly, for the detection of cow ear tags, the lightweight Small-YOLOV5s is proposed, and then a differentiable binarization network (DBNet) combined with a convolutional recurrent neural network (CRNN) is used to achieve the recognition of the numbers on ear tags. The experimental results demonstrated notable improvements: Compared to those of YOLOV5s, Small-YOLOV5s enhanced recall by 1.5%, increased the mean average precision by 0.9%, reduced the number of model parameters by 5,447,802, and enhanced the average prediction speed for a single image by 0.5 ms. The final accuracy of the ear tag number recognition was an impressive 92.1%. Moreover, this study introduces two standardized experimental datasets specifically designed for the ear tag detection and recognition of dairy cows. These datasets will be made freely available to researchers in the global dairy cattle community with the intention of fostering intelligent advancements in the breeding industry.


Assuntos
Agricultura , Reconhecimento Psicológico , Animais , Feminino , Bovinos , Fazendas , Indústrias , Inteligência
3.
J Cell Mol Med ; 28(6): e18115, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38436544

RESUMO

Ovarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Proteínas Ribossômicas , Feminino , Humanos , Apoptose/genética , Proliferação de Células/genética , Neoplasias Ovarianas/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo , Fator de Ligação a CCCTC/genética
4.
ACS Nano ; 18(6): 4944-4956, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38301227

RESUMO

A breakthrough in the performance of bionic optical structures will only be achieved if we can obtain an in-depth understanding of the synergy mechanisms operating in natural optical structures and find ways to imitate them. In this work, inspired by feline eyes, an optical substrate that takes advantage of a synergistic effect that occurs between resonant and reflective structures was designed. The synergistic effect between the reflective and resonant components leads to a Raman enhancement factor (EF) of 1.16 × 107, which is much greater than that achieved using the reflective/resonant cavities on their own. Finite-difference time-domain (FDTD) simulations and experimental results together confirm that the mechanism of this synergistic effect is achieved by realizing multiple reflections and repeated absorptions of light, generating a strong local electric field. Thus, a 2-3 order of magnitude increase in sensitivity could be achieved. More importantly, with the homemade centrifugal device, above optical substrates were further used to develop a rapidly highly sensitive household health monitoring system (detection time <3 min). It can thus be used to give early warning of acute diseases with high risk (e.g., acute myocardial infarction (AMI) and cerebral peduncle). Due to the good reusability and storability (9% and 8% reduction in EF after washing 30 times and 9 months of storage, respectively) of the substrates, the substrates thus reduce detection costs (to ∼$1), making them much cheaper to use than the current gold-standard methods (e.g., ∼$16 for gout detection).


Assuntos
Análise Espectral Raman , Gatos , Animais , Humanos , Análise Espectral Raman/métodos , Doença Crônica
5.
Sci Rep ; 14(1): 3881, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365883

RESUMO

Primary angle closure disease (PACD) is a major cause of blindness worldwide. It has a high prevalence in East Asia, especially in China, which leads to a higher incidence of blindness than open-angle glaucoma. The aim of this study was to directly observe the circumlental space (CLS) in laser peripheral iridotomized eyes with PACD and to determine whether this structure plays a role in the pathogenesis of PACD. Fifty eyes of 50 patients with PACD, who had received laser peripheral iridotomy performed with neodymium:yttrium-aluminum-garnet were recruited from glaucoma clinics from March 2021 to May 2022, including 17 primary angle closure suspect (PACS), 16 primary angle closure (PAC) and 17 primary angle closure glaucoma (PACG). They were classified into two groups based on whether the ciliary process and the crystalline lens equator were in contact using slit-lamp photograph: the attached group and the unattached group. The demographic, clinical characteristics and anterior segment parameters measured from ultrasound biomicroscopy were compared between the attached group and the unattached group. Thirty-three eyes were assigned to the attached group and 17 eyes belonged to the unattached group. In the unattached group, the mean CLS was 0.10 ± 0.07 mm. No significant differences were identified between the different diagnosis groups in age, sex, best-corrected visual acuity, intraocular pressure, white-to-white, axial length, central corneal thickness, anterior chamber depth, flat keratometry, steep keratometry or iridotomy diameter (p > 0.05). The unattached group had shorter trabecular-ciliary process distance (p = 0.021) and larger ciliary process area (p = 0.001) compared with the attached group. Small CLS and its potential effect (partial ciliary block) might be considered as one of the mechanisms of PACD.


Assuntos
Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Humanos , Segmento Anterior do Olho/patologia , Iris/cirurgia , Iris/patologia , Glaucoma de Ângulo Aberto/patologia , Glaucoma de Ângulo Fechado/patologia , Câmara Anterior/diagnóstico por imagem , Câmara Anterior/cirurgia , Câmara Anterior/patologia , Pressão Intraocular , Cegueira/patologia
6.
Heliyon ; 10(4): e25644, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38370173

RESUMO

The purpose of this work is to comprehensively understand the adaptive response of multiple epigenetic modifications on gene expression changes driven by exercise. Here, we retrieved literatures from publications in the PubMed and Web of Science Core Collection databases up to and including October 15, 2023. After screening with the exclusion criteria, 1910 publications were selected in total, comprising 1399 articles and 511 reviews. Specifically, a total of 512, 224, and 772 publications is involved in DNA methylation, histone modification, and noncoding RNAs, respectively. The correlations between publication number, authors, institutions, countries, references, and the characteristics of hotspots were explored by CiteSpace. Here, the USA (621 publications) ranked the world's most-influential countries, the University of California System (68 publications) was the most productive, and Tiago Fernandes (14 publications) had the most-published publications. A comprehensive keyword analysis revealed that cardiovascular disease, cancer, skeletal muscle development, and metabolic syndrome, and are the research hotspots. The detailed impact of exercise was further discussed in different aspects of these three categories of epigenetic modifications. Detailed analysis of epigenetic modifications in response to exercise, including DNA methylation, histone modification, and changes in noncoding RNAs, will offer valuable information to help researchers understand hotspots and emerging trends.

7.
Ophthalmol Ther ; 13(1): 113-125, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37874535

RESUMO

INTRODUCTION: This study explored the current views of ophthalmologists in China on the preferred strategy and the primary influencing factors in managing primary angle-closure suspect (PACS). METHODS: An online survey was distributed via WeChat to ophthalmologists working in hospitals at all levels throughout China to investigate the optimal management strategy and factors influencing the strategy for treating PACS from February to March 2023. Management strategies examined included regular observation (RO), laser peripheral iridectomy (LPI), and phacoemulsification with intraocular lens implantation (PEI). The study explored the factors that influenced clinical decision-making processes and collected demographic information from the respondents for analysis. RESULTS: A total of 1009 ophthalmologists responded; 442 responders considered RO as a reasonable option for patients with PACS, while the majority opted for more positive treatments, with 460 choosing LPI and 107 selecting PEI. Further grouping analysis revealed significant differences between tertiary and lower-level hospitals (P < 0.01) and between public and private hospitals (P < 0.05). Significant differences were found among resident, attending, and senior doctors and between northern and southern hospitals. The top three considerations for ophthalmologists who selected RO were ultrasound biomicroscopy (UBM) without pupillary block, absence of a family history of glaucoma, and good compliance with regular follow-up. For LPI, the factors were UBM indicating pupillary block, glaucoma symptoms, and poor compliance with regular follow-up. For PEI the factors were age, family history of glaucoma, and poor compliance with regular follow-up. CONCLUSION: The majority of ophthalmologists prefer aggressive treatments such as LPI or PEI over RO when dealing with patients with PACS. Disparity existed among ophthalmologists based on their level of experience, hospital ownership and level, and geographical location. The survey underscores the complexity and multifactorial nature of PACS management and highlights the need for further research and standardization of treatment protocols to ensure optimal patient outcomes.

8.
Clin Toxicol (Phila) ; 61(11): 961-967, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37999959

RESUMO

BACKGROUND: Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. PURPOSE: This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. METHODS: We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. RESULTS: There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. CONCLUSION: Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.


Assuntos
Óxido Nitroso , Deficiência de Vitamina B 12 , Masculino , Feminino , Adulto Jovem , Humanos , Adolescente , Adulto , Óxido Nitroso/efeitos adversos , Estudos Retrospectivos , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/complicações , Vitaminas/uso terapêutico
9.
Animals (Basel) ; 13(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38003075

RESUMO

To achieve rapid and precise target counting, the quality of target detection serves as a pivotal factor. This study introduces the Sheep's Head-Single Shot MultiBox Detector (SH-SSD) as a solution. Within the network's backbone, the Triple Attention mechanism is incorporated to enhance the MobileNetV3 backbone, resulting in a significant reduction in network parameters and an improvement in detection speed. The network's neck is constructed using a combination of the Spatial Pyramid Pooling module and the Triple Attention Bottleneck module. This combination enhances the extraction of semantic information and the preservation of detailed feature map information, with a slight increase in network parameters. The network's head is established through the Decoupled Head module, optimizing the network's prediction capabilities. Experimental findings demonstrate that the SH-SSD model attains an impressive average detection accuracy of 96.11%, effectively detecting sheep's heads within the sample. Notably, SH-SSD exhibits enhancements across various detection metrics, accompanied by a significant reduction in model parameters. Furthermore, when combined with the DeepSort tracking algorithm, it achieves high-precision quantitative statistics. The SH-SSD model, introduced in this paper, showcases commendable performance in sheep's head detection and offers deployment simplicity, thereby furnishing essential technical support for the advancement of intelligent animal husbandry practices.

10.
Int J Mol Sci ; 24(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37894939

RESUMO

The Hippo pathway mediates renal maladaptive repair after acute kidney injury (AKI), which has been considered a driving force in the progression to chronic kidney disease (CKD). LATS2, a core kinase of the Hippo pathway, exerts non-Hippo-dependent functions in the regulation of the cell cycle and cell fate, providing new insights into AKI and further repair. However, its role remains unknown. Here, we utilized a proximal tubular Lats2 conditional knockout mouse strain (Lats2-CKO) to evaluate the effect of LATS2 deficiency on ischemia/reperfusion-induced AKI-to-CKD transition. Lats2-CKO mice presented with more severe tubular maladaptive repair, inflammatory infiltration, interstitial fibrosis, and apoptosis following AKI. Importantly, we discovered that Lats2 ablation caused the activation of p53, with increased levels of cellular apoptotic molecules (p21, Bax, and cleaved caspase-3), and decreased levels of anti-apoptotic molecules (Bcl-2 and Bcl-xL). Pifithirin-α (p53 inhibitor) effectively attenuated renal fibrosis, inflammation, and apoptosis in Lats2-CKO mice after AKI. Consistently, in vitro Lats2 overexpression decreased p53, p21, Bax and cleaved caspase 3 expression after hypoxia/reoxygenation (H/R) treatment. Of note, the phosphorylation of MDM2, which promotes the ubiquitination degradation of p53, at site Ser186 was decreased in Lats2-CKO kidneys, but increased by Lats2 overexpression in vitro. Therefore, LATS2 deficiency aggravated ischemia/reperfusion injury (IRI)-induced maladaptive repair via regulating the tubular MDM2-p53 axis in AKI-to-CKD transition.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Traumatismo por Reperfusão , Animais , Camundongos , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Apoptose , Proteína X Associada a bcl-2/metabolismo , Rim/metabolismo , Camundongos Endogâmicos C57BL , Insuficiência Renal Crônica/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
11.
Dev Cell ; 58(21): 2326-2337.e5, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37863040

RESUMO

High-density lipoprotein (HDL) metabolism is regulated by complex interplay between the scavenger receptor group B type 1 (SR-BI) and multiple signaling molecules in the liver. Here, we show that lipocalin-2 (Lcn2) is a key regulator of hepatic SR-BI, HDL metabolism, and atherosclerosis. Overexpression of human Lcn2 in hepatocytes attenuates the development of atherosclerosis via SR-BI in western-diet-fed Ldlr-/- mice, whereas hepatocyte-specific ablation of Lcn2 has the opposite effect. Mechanistically, hepatocyte Lcn2 improves HDL metabolism and alleviates atherogenesis by blocking Nedd4-1-mediated SR-BI ubiquitination at K500 and K508. The Lcn2-improved HDL metabolism is abolished in mice with hepatocyte-specific Nedd4-1 or SR-BI deletion and in SR-BI (K500A/K508A) mutation mice. This study identifies a regulatory axis from Lcn2 to HDL via blocking Nedd4-1-mediated SR-BI ubiquitination and demonstrates that hepatocyte Lcn2 may be a promising target to improve HDL metabolism to treat atherosclerotic cardiovascular diseases.


Assuntos
Aterosclerose , Lipoproteínas HDL , Camundongos , Humanos , Animais , Lipoproteínas HDL/metabolismo , Lipocalina-2/genética , Lipocalina-2/metabolismo , Hepatócitos/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Fígado/metabolismo , Antígenos CD36/metabolismo
12.
BMC Ophthalmol ; 23(1): 373, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697299

RESUMO

BACKGROUND: Tentorial dural arteriovenous fistulas (TDAVFs) are abnormal shunts between meningeal arteries and the intradural venous system located in the tentorial dura mater, which typically manifest with haemorrhage or progressive neurological disorders. TDAVFs with pure ocular presentation have been rarely reported. CASE PRESENTATIONS: The case of a 56-year-old man presented with unilateral eye redness, proptosis and elevated intraocular pressure was reported herein, which was caused by a TDAVF. The fistula was fed by the left posterior cerebral artery and posterior meningeal artery. The drainage was into the basal vein and internal cerebral veins, which led the arterial blood flow forward to the left superior ophthalmic vein directly. The redundant blood flow caused the rise of episcleral venous pressure, leading to the clinical presentations. Gamma knife radiosurgery was performed then considering the delicate vascular structure and its deep location. The corkscrew hyperaemia was gradually alleviated after the surgery, but the intraocular pressure remained elevated at follow-ups. CONCLUSION: Dural arteriovenous fistulas which are not directly connected to cavernous sinus could cause ocular presentations like proptosis, eye redness and ocular hypertension.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Exoftalmia , Hipertensão , Hipertensão Ocular , Masculino , Humanos , Pessoa de Meia-Idade , Olho , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Exoftalmia/diagnóstico , Exoftalmia/etiologia
13.
Int J Infect Dis ; 135: 5-7, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37327856

RESUMO

Mycobacterium iranicum is characterized by rapid growth and orange-pigmented scotochromogenic colonies. However, it is uncommon for M. iranicum to invade the central nervous system. A man nearly 60 years old was referred to our hospital because of a seizure and unconsciousness. After admission, the patient had fever and dizziness without obvious abnormalities in the cerebrospinal fluid, except for an increase in neutrophils. Metagenomic next-generation sequencing and DNA testing were positive for M. iranicum. The patient was treated with imipenem, minocycline, moxifloxacin, and linezolid, and he gradually recovered during follow-up.


Assuntos
Epilepsia , Meningites Bacterianas , Mycobacteriaceae , Infecções por Mycobacterium , Masculino , Humanos , Pessoa de Meia-Idade , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico
14.
Front Bioeng Biotechnol ; 11: 1196043, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37260827

RESUMO

Tetrodotoxin (TTX) could result in serious diseases due to its extremely high neurotoxicity. Thus, it is of great importance to measure TTX for food safety. In this study, an anti-TTX monoclonal antibody with good specificity and high affinity was used to develop the immunochromatographic test strips (ICTS). Gold nanoflower (AuNF) with multiple branches and latex microsphere (LM) with large particle size as signal reporters were employed for improving the sensitivity of test strips. Both AuNF and LM probes are stable, and the developed ICTS were specific to TTX, demonstrating no cross-reactivity with other marine toxins. The linear range of AuNF- and LM-based strips for TTX was 9.49-330.98 ng/mL and 5.40-443.19 ng/mL, respectively. The limit of detection (LOD) of AuNF- and LM-based strips was determined to be 9.49 ng/mL and 5.40 ng/mL, respectively. In summary, the developed ICTS based on AuNF and LM signal probes displayed enhancement of sensitivity and provided rapid and specific detection of TTX.

15.
BMC Ophthalmol ; 23(1): 202, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37158871

RESUMO

BACKGROUND: Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon fundus disease characterized by perivenous aggregations of pigment clumps and retinochoroidal atrophy distributed along the retinal veins. We report a Chinese female case of unilateral PPRCA with acute angle-closure glaucoma (AACG). CASE PRESENTATION: A 50-year-old Chinese female presented with vision loss and elevated intraocular pressure (IOP) in the right eye and then underwent trabeculectomy. She referred to our clinic for further evaluation and treatment. The funduscopic examination revealed grayish retinochoroidal atrophy and osteocyte-like pigment clumping lesions along the retinal veins and peripapillary preretinal hemorrhage in the right eye. The patient also presented with AACG in the same eye on the basis of past medical history of acute attack, shallow anterior chamber depth (ACD), narrow angle showed by ultrasound biomicroscopy (UBM) and glaucomatous neuropathy identified by optical coherence tomography (OCT). Other examinations like fluorescein fundus angiography (FFA), electroretinogram (ERG) and electrooculography (EOG) all confirmed the aforementioned diagnose. CONCLUSION: PPRCA is a rare disease, uncommon in females and symmetrical in both eyes. We present a rare case of unilateral PPRCA accompanied with AACG.


Assuntos
Glaucoma de Ângulo Fechado , Glaucoma , Feminino , Humanos , Pessoa de Meia-Idade , Glaucoma de Ângulo Fechado/diagnóstico , Doença Aguda , Atrofia , Fundo de Olho
16.
Cell Mol Life Sci ; 80(4): 106, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36952018

RESUMO

Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a unique component of the ubiquitin-proteasome system (UPS), which has multiple activities in maintaining intracellular ubiquitin levels. We previously reported the aberrant low expression of UCHL1 in podocytes of non-immune complex-mediated glomerulonephritis, and recent studies indicate that anti-UCHL1 antibody was responsible for the refractory minimal change disease (MCD), but the specific effect of UCHL1 to the podocytopathy has not been determined. Therefore, we generated podocyte-specific UCHL1 gene knockout (UCHL1cre/cre) rats model. Podocyte-specific UCHL1 knockout rats exhibited severe kidney damage, including segmental/global glomerulosclerosis, kidney function damage and severe proteinuria, compared with littermate control. Subsequently, by carrying out mass spectrometry analysis of isolated glomeruli of rats, abnormal protein accumulation of ECM-receptor Interaction was found in UCHL1cre/cre rats. Mechanistic studies in vivo and in vitro revealed that aberrant protein accumulation after UCHL1 deficiency induced endoplasmic reticulum (ER) stress, unfolded protein reaction (UPR) to reduce the protein level of podocyte skeleton proteins, and CHOP mediated apoptosis as well, which related to the dysfunction of the ubiquitin-proteasome system with decreased free monomeric ubiquitin level, thereby affecting protein ubiquitination and degradation. In addition, inhibition of ER stress by 4-PBA could attenuate the degree of ER stress and podocyte dysfunction. Our study indicates that UCHL1 is a potential target for preventing podocytes injury in some non-immune complex-mediated glomerulopathy.


Assuntos
Nefropatias , Podócitos , Ratos , Animais , Podócitos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Ubiquitinação , Estresse do Retículo Endoplasmático/genética , Nefropatias/metabolismo , Ubiquitina Tiolesterase/metabolismo
17.
Am J Clin Pathol ; 160(2): 144-149, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36933186

RESUMO

OBJECTIVES: Amyloid light chain (AL)-κ and AL-λ share common histopathologic changes; however, the potential difference in clinical manifestations, histologic findings, and clinical significance between the 2 subtypes remain unclear. METHODS: In a retrospective study, 94 kidney biopsies for AL amyloidosis were evaluated using the composite scarring injury score (CSIS) and amyloid score (AS). Results were then compared between AL-κ and AL-λ. RESULTS: Comparing AS and CSIS between AL-κ and AL-λ, the AS was significantly higher in AL-κ than in AL-λ, with 2 components of AS (capillary wall and vascular amyloid) scoring higher in AL-κ than in AL-λ, while mesangial and interstitial ASs were similar in the 2 cohorts. In addition, the proportion of periodic acid-Schiff strong-staining amyloid in AL-κ was markedly higher than in AL-λ. There was no significant difference in CSIS and its components between the 2 subtypes of AL amyloidosis. CONCLUSIONS: Overall, AL-κ presents with higher serum creatinine and a higher AS score than AL-λ at biopsy, which may indicate a worse prognosis and be an important reference for clinical management.


Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Estudos Retrospectivos , Amiloidose/diagnóstico , Amiloidose/patologia , Amiloide , Cadeias lambda de Imunoglobulina , Corantes
18.
Neurosci Lett ; 808: 137189, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-36921668

RESUMO

OBJECTIVE: Insufficient sleep affects cognitive function, but the underlying mechanism and potential protective ways are yet to be fully understood. This study aimed to explore the influence of chronic sleep restriction (CSR) on the insulin-like growth factor-1 (IGF-1) signaling pathway, and whether down-regulating IGF-1 signaling pathway would modulate amyloid-ß (Aß) peptides metabolism and its cortical deposition after CSR. Methods 8-week IGF-1R+/- mice and wild-type (WT) C57BL/6 (C57) mice were divided into four groups: IGF-1R+/- CSR (MUSR), IGF-1R+/- control (MUCO), C57 CSR (C57SR) and C57 control (C57CO). CSR model was established by application of slowly rotating drum for 2 months. Body weight and Lee's index were measured. The level of IGF-1 in plasma was measured by enzyme linked immunosorbent assay (ELISA). Aß accumulation was detected by immunofluorescence. The expressions of amyloid precursor protein (APP), ß-site amyloid precursor protein-cleaving enzyme-1 (BACE-1) and C99 were detected using western-blot (WB). Results Two-way ANOVA showed genotypic effect was significant on body weight and Lee's index. Neither treatment effect nor interaction reached significant difference on body weight and Lee's index. The level of IGF-1 in plasma was significantly decreased in C57SR compared with C57CO. Besides, compared with C57CO, Aß was markedly accumulated in frontal cortex, in parallel with increased expressions of BACE-1 and C99, and with no difference of APP in C57SR group. Further, no significant changes of Aß, BACE-1, C99 and APP were detected in MUSR compared with MUCO. Conclusions This study showed that CSR could induce the decrease of circulating IGF-1 in mice. By using the IGF-1R+/- mice, we found that down-regulating IGF-1R could reduce Aß deposition in mice frontal cortex after CSR via inhibiting BACE-1 protein expression and activity, which were independent of the changes of body weight and Lee's index. These findings indicate that the blockage of IGF-1 signaling pathway might be a protection mechanism for alleviating the impact of CSR.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Camundongos , Animais , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Camundongos Endogâmicos C57BL , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Privação do Sono/metabolismo , Doença de Alzheimer/metabolismo
19.
J Diabetes Res ; 2023: 1901105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776229

RESUMO

The loss of podocyte is crucial for diagnosis and prognosis of diabetic kidney disease, whereas commonly two-dimensional methods for quantifying podocyte number existed with issues of low fidelity and accuracy. In this study, clear, unobstructed brain imaging cocktails and computational analysis (CUBIC), one of three-dimensional optical clearing approaches, was used which combines tissue clearing, immunolabeling, and a light-sheet microscope to image and evaluate podocytes in C57BL/6 (C57) and db/db mice. We discovered that 77 podocytes per glomerulus were in C57 mice. On the subject of db/db mice, there were 74 podocytes by the age of 8 w, 72 podocytes by the age of 12 w, and 66 podocytes by the age of 16 w, compared with 76 podocytes in the control group, suggesting that there was a significant decrease in podocyte number in db/db mice with the age of 16 w, showing a trend which positively correlated to the deterioration of kidney function. Sample size estimation using the PASS software revealed that taking 5%, 7.5%, and 10% of the mean podocyte number per glomerulus as the statistical allowable error and 95% as total confidence interval, 33, 15, and 9 glomeruli were independently needed to be sampled in C57 mice to represent the overall glomeruli to calculate podocyte number. Furthermore, in the control group of db/db mice, 36, 18, and 11 glomeruli were needed, compared with 46, 24, and 14 glomeruli in db/db mice by the age of 8 w, 43, 21, and 12 glomeruli by the age of 12 w, and 52, 27, and 16 by the age of 16 w. These findings indicated that precise quantification of podocyte number could judge the progression of diabetic kidney disease. In addition, a small number of glomeruli could be actually representative of the whole sample size, which indicated apparent practicability of CUBIC for clinical use.


Assuntos
Nefropatias Diabéticas , Podócitos , Camundongos , Animais , Tamanho da Amostra , Camundongos Endogâmicos C57BL , Glomérulos Renais , Camundongos Endogâmicos
20.
Front Neurol ; 14: 1099077, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36779053

RESUMO

Background: Nitrous oxide (N2O) is an increasingly popular recreational drug. N2O irreversibly disturbs the metabolism of vitamin B12, resulting in a functional deficiency. Vitamin B12 is vital for myelin synthesis and its deficiency primarily produces neurological complications. Inhaling N2O is more common and neurological complications are more evident than before. Case presentation: We report a young man who developed progressive limb numbness and unsteady walking after N2O abuse. The dominant diagnosis was subacute combined degeneration of the spinal cord (SCD). The patient was admitted to the hospital and given adenosylcobalamin treatment, but his symptoms progressed significantly from before and he developed acute cognitive impairment. After methylprednisolone combined with vitamin B12 treatment, symptoms significantly improved. Conclusion: Clinicians need to understand the presentation and treatment of SCD caused by N2O abuse. When symptoms progress despite conventional vitamin B12 therapy, the combination of methylprednisolone and vitamin B12 may be considered.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...