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1.
Food Chem ; 398: 133862, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35963220

RESUMO

In this study, co-assembled protein-polysaccharide complexes (ZCs) were prepared by fixing zein nanoparticles at the fibrillar carboxymethyl cellulose (CMC) by pH-driven anti-solvent precipitation. The complexation boosted the dispersity of zein from 17.3% to 88.6%. Scanning electron microscopy and atomic force microscopy confirmed the formation of network structures where the fibrous polysaccharides inserted into the interval of granular proteins. Circular dichroism spectrum, fluorescence spectrum, and X-ray diffraction verified the electrostatic interaction pattern between zein and CMC. Besides, the ZCs presented favorable amphiphilic properties, and the electrostatic interaction between zein and CMC can be fine-tuned by the substitution degree (DS) of carboxymethyl in CMC. Therefore, the Pickering emulsions stabilized by ZCs had controllable size and long-term stability using DS as a stimulus. Our study offers a novel strategy developing bio-based materials as novel stabilizers of Pickering emulsions.


Assuntos
Nanopartículas , Zeína , Carboximetilcelulose Sódica/química , Emulsões/química , Nanopartículas/química , Tamanho da Partícula , Zeína/química
2.
Food Chem ; 398: 133847, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35969997

RESUMO

In this study, waxy corn starch (WCS) was enzymatically modified by amylosucrase, followed by complexation with lauric acid (LA) to produce starch-lipid complexes. Compared to the native WCS with average chain length (CL¯) of 25.4, the amylosucrease-modified WCSs showed a significantly higher CL¯ ranging from 29.3 to 52.5. The complexation with lauric acid inhibited the reassociation of starch chains, producing V-type complexes with crystallinity reached as much as 42.4 %. Besides, the melting of V-type complexes presented endothermic peaks at Tp of 55.1-60.4 °C, and thermal stability of V-type complexes had a negative correlation with the V-type crystallinity. In vitro digestion implies that the formation of V-type complexes gradually increased the content of rapidly digestible starch and accordingly decreased the content of resistant starch. This study may provide an efficient technology to produce V-type starch-lipid complexes with controllable physical and digestion properties using waxy starch as substrate.


Assuntos
Amido , Zea mays , Amilopectina/química , Amido/química , Zea mays/química
3.
Stem Cell Res Ther ; 13(1): 450, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064453

RESUMO

BACKGROUND: Erectile dysfunction (ED), as one of the most prevalent consequences in male diabetic patients, has a serious impact on men's physical and mental health, and the treatment effect of diabetic mellitus erectile dysfunction (DMED) is often worse. Therefore, the development of a novel therapeutic approach is urgent. As stem cells with high differentiation potential, human umbilical cord mesenchymal stem cells (HUCMSCs) have been widely used in the treatment of diseases in other systems, and are expected to be a promising strategy for the treatment of DMED. In this study, we investigated the role of HUCMSCs in managing erectile function in rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and compared the effects of two different injection methods. METHODS: T1DM and T2DM ED rats were given labelled HUCMSCs by corpus cavernosum injection and tail vein injection, respectively. ICP and MAP were monitored simultaneously by electrical stimulation four weeks after injection to indicate the erectile function of rats. To track the development and colonisation capabilities of stem cells, we performed EdU assay with penile tissue. The histological changes of the penis were observed by hematoxylin-eosin staining, and Masson's trichrome staining was conducted to evaluate the smooth muscle content and the degree of fibrosis in the rat penis. Then, we employed specific kits to measure the level of NO, cGMP, MDA, SOD and Fe in penis. Electron transmission microscopy was implemented to observe morphology of mitochondria. Besides, western blot and immunofluorescence staining were performed to demonstrate the expression of ferroptosis-related genes. RESULTS: We found that HUCMSCs improved erectile function in T1DM and T2DM ED rats, with no difference in efficacy between corpus cavernosum injection and tail vein injection. The EdU assay revealed that only a tiny percentage of HUCMSCs colonised the corpus cavernosum, while smooth muscle in the penis expanded and collagen decreased following HUCMSC injection. Moreover, the levels of oxidative stress in the penis of the rats given HUCMSCs were dramatically reduced, as was the tissue iron content. HUCMSCs normalised mitochondrial morphology within corpus cavernosum smooth muscle cells (CCSMCs), which were characteristically altered by high glucose. Furthermore, the expression of ferroptosis inhibitory genes SLC7A11 and GPX4 was obviously elevated in CCSMCs after stem cell management, but the abundances of ACSL4, LPCAT3 and ALOX15 showed the polar opposite tendency. CONCLUSIONS: HUCMSCs can effectively and safely alleviate erectile dysfunction in T1DM and T2DM ED rats, while restoring erectile function by attenuating diabetes-induced ferroptosis in CCSMCs. Additionally, this study provides significant evidence for the development of HUCMSCs as a viable therapeutic strategy for DMED.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Disfunção Erétil , Ferroptose , Células-Tronco Mesenquimais , Animais , Disfunção Erétil/terapia , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Cordão Umbilical/metabolismo
4.
Oxid Med Cell Longev ; 2022: 1274550, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062196

RESUMO

Traumatic brain injury (TBI) is a serious health issue with a high incidence, high morbidity, and high mortality that poses a large burden on society. Further understanding of the pathophysiology and cell death models induced by TBI may support targeted therapies for TBI patients. Ferroptosis, a model of programmed cell death first defined in 2012, is characterized by iron dyshomeostasis, lipid peroxidation, and glutathione (GSH) depletion. Ferroptosis is distinct from apoptosis, autophagy, pyroptosis, and necroptosis and has been shown to play a role in secondary brain injury and worsen long-term outcomes after TBI. This review systematically describes (1) the regulatory pathways of ferroptosis after TBI, (2) the neurobiological links between ferroptosis and other cell death models, and (3) potential therapies targeting ferroptosis for TBI patients.


Assuntos
Lesões Encefálicas Traumáticas , Ferroptose , Apoptose , Morte Celular , Humanos , Peroxidação de Lipídeos
6.
Geriatr Orthop Surg Rehabil ; 13: 21514593221124415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051508

RESUMO

Study Design: A meta-analysis. Objective: Anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) are widely used in the treatment of cervical spondylotic myelopathy (CSM). However, the clinical outcomes and complications between ACDF and ACCF treating multi-level CSM remain poorly understood. Thus, we performed a meta-analysis to compare the clinical outcomes and complications of the two procedures in the treatment of 3-level and 4-level CSM. Methods: An extensive search of the literature was performed in the English databases of PubMed, Embase, and Cochrane Library and the Chinese databases of CNKI and WANFANG. We collected factors, including demographic data, surgical factors, and complications. Data analysis was conducted with RevMan 5.3 and STATA 12.0. Results: Finally, 14 articles (5429 patients) were included in our study. No significant difference was found in preoperative and 3-month follow-up Japanese Orthopedic Association (JOA) scores, neck disability index, preoperative C2-C7, segmental angle, operation time, as well as the number of dysphagia, hoarseness, cerebral fluid leakage, infection, epidural hematoma, axial pain, hardware breakage, and pseudarthrosis between ACDF and ACCF. However, our findings showed that blood loss (P < 0.00001), the number of total complications (P < 0 .00001), C5 palsy (P = 0.0004), graft dislodgement (P = 0.02), graft subsidence (P = 0.0003), and revision surgery (P = 0.0008) in ACDF were significantly less than in ACCF. Additionally, postoperative and change of C2-C7 (P < 0.00001), segment angle (P < 0.00001), and fusion rate (P = 0.001) in ACDF were significantly higher than in ACCF. Post-operative JOA in ACDF was significantly higher than in ACCF (P = 0.02). Conclusions: Although the clinical efficacy of both surgeries was similar, ACDF was superior to ACCF in the reconstruction of cervical lordosis and the number of complications in the treatment of 3-level and 4-level CSM.

7.
World J Mens Health ; 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-36047071

RESUMO

PURPOSE: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). MATERIALS AND METHODS: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. RESULTS: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFß1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. CONCLUSIONS: RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

8.
CNS Neurosci Ther ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047338

RESUMO

BACKGROUND: Current evidence for the efficacy of pharmacological treatment in improving cognitive function is absent. Recent studies have reported that 3-n-butylphthalide (NBP) has a positive effect on improving cognitive impairment; however, its clinical efficacy and safety is unclear. Therefore, we conducted a meta-analysis to assess its efficacy and safety for cognitive impairment. METHODS: We systematically searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases, and two reviewers independently screened and extracted the data from included studies. We synthesized the data using the Review Manager Software version 5.3. RESULTS: We included six randomized clinical trials (RCTs), encompassing 851 patients with cognitive impairment. The results showed that NBP improved cognitive impairment. Specifically, the clinical efficacy was better than that in the control group, with better performance in improving the Mini-Mental State Examination and the Montreal Cognitive Assessment scores, while decreasing the Alzheimer's Disease Assessment Scale-Cognitive subscale and the Clinician's Interview-Based Impression of Change plus caregiver input scores. There was no significant difference in the incidence of adverse events between both groups. CONCLUSION: The NBP is effective and safe in improving cognitive impairment; however, more high-quality RCTs are needed to confirm these findings.

9.
Nat Commun ; 13(1): 5284, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36075929

RESUMO

Myelofibrosis is a rare myeloproliferative neoplasm (MPN) with high risk for progression to acute myeloid leukemia. Our integrated genomic analysis of up to 933 myelofibrosis cases identifies 6 germline susceptibility loci, 4 of which overlap with previously identified MPN loci. Virtual karyotyping identifies high frequencies of mosaic chromosomal alterations (mCAs), with enrichment at myelofibrosis GWAS susceptibility loci and recurrently somatically mutated MPN genes (e.g., JAK2). We replicate prior MPN associations showing germline variation at the 9p24.1 risk haplotype confers elevated risk of acquiring JAK2V617F mutations, demonstrating with long-read sequencing that this relationship occurs in cis. We also describe recurrent 9p24.1 large mCAs that selectively retained JAK2V617F mutations. Germline variation associated with longer telomeres is associated with increased myelofibrosis risk. Myelofibrosis cases with high-frequency JAK2 mCAs have marked reductions in measured telomere length - suggesting a relationship between telomere biology and myelofibrosis clonal expansion. Our results advance understanding of the germline-somatic interaction at JAK2 and implicate mCAs involving JAK2 as strong promoters of clonal expansion of those mutated clones.


Assuntos
Transtornos Mieloproliferativos , Mielofibrose Primária , Células Germinativas , Haplótipos , Humanos , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/genética , Mielofibrose Primária/genética
10.
Int J Mol Sci ; 23(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076917

RESUMO

Neurological dysfunctions commonly occur after mild or moderate traumatic brain injury (TBI). Although most TBI patients recover from such a dysfunction in a short period of time, some present with persistent neurological deficits. Stress is a potential factor that is involved in recovery from neurological dysfunction after TBI. However, there has been limited research on the effects and mechanisms of stress on neurological dysfunctions due to TBI. In this review, we first investigate the effects of TBI and stress on neurological dysfunctions and different brain regions, such as the prefrontal cortex, hippocampus, amygdala, and hypothalamus. We then explore the neurobiological links and mechanisms between stress and TBI. Finally, we summarize the findings related to stress biomarkers and probe the possible diagnostic and therapeutic significance of stress combined with mild or moderate TBI.


Assuntos
Lesões Encefálicas Traumáticas , Encéfalo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Hipocampo , Humanos
11.
ACS Omega ; 7(36): 32432-32441, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36120051

RESUMO

In a spontaneous coal combustion environment and in the coal chemical process, multiple gases, such as CH4, H2, and CO, coexist, and explosion accidents are prone to occur. The causes of these disasters and the explosion characteristics are key to formulating preventive measures. To explore the effect of H2/CO on the explosion pressure and thermal behavior of methane-air, CH4 with initial volume fractions of 7, 9.5, and 12%, which correspond to three states of oxygen enrichment, equivalence ratio, and oxygen depletion, was selected. Moreover, a mixed fuel system is composed of H2/CO with different volume ratios. A 20 L spherical gas explosion experimental system was used to test the peak explosion overpressure P max, the maximum explosion overpressure rise rate (dP/dt)max, and the corresponding time parameters of the H2/CO-CH4 mixed system. Combined with the thermodynamic calculation model, laminar burning velocity S L, explosion heat loss q tra, and other parameters were obtained. The results show that due to the existence of the damping effect, CO has the dual characteristic of promoting or weakening methane explosions. Compared with CO, the effect of H2 on the methane explosion is more significant, and the improvement or weakening of the laminar combustion rate of the reaction system by CO "lags" behind that of H2. The heat loss in the process of a gas explosion is affected by factors such as the heat release rate, the propagation speed of the combustion wave, and the heat dissipation effect of the container wall. When H2/CO increases the laminar burning velocity of the mixed system, the heat loss decreases accordingly. This study also found that the laminar burning velocity model of the mixed gas based on the ideal spherical flame propagation theory is not fully applicable to the H2/CO/CH4 mixed system in a spherical closed space, and the calculation results have large errors when the mixed system is close to the upper limit of the explosion.

12.
Chin Herb Med ; 14(1): 154-165, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36120125

RESUMO

Objective: To evaluate the safety and efficacy of Compound Huangdai Tablets (Realgar-Indigo Naturalis formula, RIF) combined with all-trans retinoic acid (ATRA) to treat acute promyelocytic leukemia (APL). Methods: This study was registered in PROSPERO (CRD42018108118). The relevant literatures on RIF treatment of APL were systematically searched in the following databases: China National Knowledge Infrastructure, Wanfang, VIP Medical Information System, Chinese Biomedical Database, EMBASE, Cochrane Library, and PubMed. The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis. In addition, this study used the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL. Results: The study included 12 studies involving 775 APL patients. The Meta-analysis showed that there was no significant difference (P > 0.05) between the RIF group and the arsenic trioxide (ATO) group for primary outcomes, secondary outcomes apart from liver dysfunction. The incidence of liver dysfunction (P = 0.006) in the RIF group were significantly lower than those in the ATO group. In addition, the cost of maintenance therapy in the RIF group was significantly lower (P < 0.05) than the ATO group. Besides, the active ingredients in RIF mainly act on targets proteins such as ACHE, NCOA2, RXRA, and then play a role in the treatment of APL through regulating multiple molecular mechanisms, such as TP53 regulates transcription of cell cycle genes, nuclear receptor transcription pathway. Conclusion: There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL. The oral RIF exposed patients to less risk, offered more convenience and had lower prices. RIF can treat APL by multi-target and multi-pathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells, and so on. Therefore, oral RIF in the treatment of APL is worthy of further research and development.

13.
Sensors (Basel) ; 22(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36080926

RESUMO

A novel all-pass slot microring resonator (SMRR), intended for label-free optical biosensing based on silicon-on-insulator platforms, is proposed. The sensor consists of a bent asymmetric directional coupler and an asymmetric-slot microring waveguide. The appropriate slot width of 140 nm is identified by the three-dimensional finite-difference time-domain (3D-FDTD) method for better light-matter interaction in applications. According to numerical calculations, the SMRR sensor with a footprint of 10 µm × 10 µm has a concentration sensitivity of 725.71 pm/% for sodium chloride (NaCl) solutions. The corresponding refractive index sensitivity is 403 nm/RIU (refractive index unit), which is approximately six times greater than that of traditional microring resonator sensors. A low detection limit of 0.129% is also achieved. This SMRR is an excellent candidate for label-free optical biosensors due to its compact structure and excellent sensing capability.


Assuntos
Técnicas Biossensoriais , Refratometria , Técnicas Biossensoriais/métodos , Silício/química
14.
Lancet Reg Health West Pac ; 29: 100592, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36090701

RESUMO

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

15.
Front Neurol ; 13: 971673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090860

RESUMO

Objective: To analyze the risk factors associated with adverse events after carotid endarterectomy (CEA) in patients with unilateral severe carotid stenosis and contralateral occlusion. Methods: Patients were recruited for CEA between August 2014 and February 2020. CEA was performed under general anesthesia. The carotid clamp time (CCT; long CCT: >20 min) is defined as the period between clamp-on and clamp-off for the stenotic carotid artery. The perioperative factors and postoperative adverse events were recorded. All patients were followed up for 1 year after CEA. Results: Sixty subjects (65.8 ± 7.2 years; 54 males) were included. Patients with adverse events had significantly longer CCT than those without adverse events (60% vs. 40%, P = 0.013). Univariate logistic regression analysis showed that a history of diabetes was significantly associated with adverse events (OR, 0.190; 95% CI, 0.045-0.814; P = 0.025); long CCT was significantly associated with adverse events (OR, 8.500; 95% CI, 1.617-44.682; P = 0.011). After adjusting for confounding factors, including age, sex, BMI, diabetes, PSV, long CCT, non-use of shunt, and history of stroke or TIA, the associations between diabetes and adverse events (OR, 0.113; 95% CI, 0.013-0.959; P = 0.046) were statistically significant; the associations between long CCT and adverse events (OR, 1.301; 95% CI, 1.049-1.613; P = 0.017) were statistically significant. Conclusions: A longer carotid clamp time (>20 min) and a history of diabetes may increase the risk of adverse events in patients with unilateral severe carotid stenosis and contralateral occlusion after CEA. With good preoperative evaluation and intraoperative monitoring, the use of shunts may not be needed intraoperatively in patients with unilateral severe carotid stenosis and contralateral occlusion.

16.
Andrology ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098277

RESUMO

BACKGROUNDS: Erectile dysfunction (ED) is a common andrological disorder that tends to afflict diabetic patients, among others. Pharmacological therapy of diabetes mellitus-induced ED (DMED) is ineffective, as it is linked with smooth muscle cell loss in the corpus cavernosum. Ferroptosis is a recently identified kind of cell death evoked by lipid peroxidation, and it is connected with a number of diabetic complications. OBJECTIVES: To investigate the role of ferroptosis in DMED. MATERIALS AND METHODS: We established the rat model of DMED and conducted a combined analysis of RNA sequencing (RNA-seq) and Gene Expression Omnibus (GEO) data to identify differentially expressed genes (DEGs). Next, DMED disease targets were determined by cross-referencing DEGs and DMED-related genes in the DisGeNET, GenCLiP3, and GeneCards databases. Additionally, these targets were analyzed using "clusterProfiler" in R utilizing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. Immunohistochemistry (IHC) staining of rat penile tissues was used to validate several targets. Notably, the Cell Counting Kit-8 assay, Western blotting, oxidative stress (OS) level, and iron concentration were tested in corpus cavernosum smooth muscle cells (CCSMCs) stimulated with high glucose (HG), and treated with Ferrostatin-1 (Fer-1). RESULTS: Sixty-nine disease targets of DMED were identified. According to KEGG analysis, these targets were primarily enriched in the ferroptosis pathway. Additionally, IHC results revealed that the expression of GPX4, SLC7A11, and ACSL4 was deregulated in the DMED group compared to the control group. Significantly, HG decreased cell viability and increased OS and iron levels in CCSMCs, which could be reversed by Fer-1 treatment. DISCUSSION AND CONCLUSION: Our study revealed that ferroptosis may indeed exist in DMED. GPX4, SLC7A11, and ACSL4 all have a role in controlling the viability of CCSMCs, making them potential therapeutic targets.

17.
Theor Appl Genet ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114309

RESUMO

KEY MESSAGE: A putative candidate gene conferring resistance to SMV strain SC1 was identified on chromosome 2, and the linked marker was validated in soybean cultivars Soybean mosaic, caused by the soybean mosaic virus, is the most common disease in soybean and a significant impediment to soybean production in the Huanghuai and Yangtze River regions of China. Kefeng No.1, a soybean cultivar, showed high resistance to soybean mosaic virus strain (SC1) collected from Huanghuai and Yangtze River regions. Genetic analysis based on the Mendelian genic population derived from the cross Kefeng No.1 × Nannong 1138-2 revealed that Kefeng No.1 possesses a single dominant gene. Furthermore, genetic fine-mapping using an F2 population containing 281 individuals delimited resistant gene to a genomic region of 186 kb flanked by SSR markers BS020610 and BS020620 on chromosome 2. Within this region, there were 14 genes based on the Williams 82 reference genome. According to sequence analysis, six of the 14 genes have amino acid differences, and one of these genes is the Rsv4 allele designated as Rsc1-DR. The functional analysis of candidate genes using the bean pod mottle virus (BPMV)-induced gene silencing (VIGS) system revealed that Rsc1-DR was accountable for Kefeng No.1's resistance to SMV-SC1. Based on the genome sequence of Rsc1-DR, an Insertion/Deletion (InDel) molecular marker, JT0212, was developed and genotyped using 100 soybean cultivars, and the coincidence rate was 89%. The study enriched our understanding of the SMV resistance mechanism. The marker developed in this study could be directly used by the soybean breeders to select the genotypes with favorable alleles for making crosses, and also it will facilitate marker-assisted selection of SMV resistance in soybean breeding.

18.
Dermatol Ther ; : e15821, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114601

RESUMO

Vitiligo is a chronic treatment-resistant autoimmune disorder characterized by circumscribed depigmented maculae. This study was conducted to evaluate the efficacy and safety of tofacitinib combined with narrowband ultraviolet B (NB-UVB) phototherapy for refractory nonsegmental vitiligo. Fifteen patients with nonsegmental vitiligo resistant to conventional therapies were administered oral tofacitinib at 5 mg twice daily plus topical halometasone cream, tacrolimus 0.1% ointment, or pimecrolimus cream twice daily and NB-UVB three times per week for 16 weeks. The control group comprised 19 patients with nonsegmental vitiligo treated with topical drugs plus NB-UVB same as the combination group. Treatment efficacy was measured by the percentage of repigmentation of vitiligo lesions at 4th, 8th, 12th, and 16th week after beginning treatment. From 8th week, the repigmentation level was significantly higher in the combination group than in the controls. From 4th week, the response rate was significantly higher in the combination group than in the controls. Only one patient in the combination group reported mild pain in the hand and foot joints, but the pain subsided with cessation of therapy. No other severe adverse effects occurred. So, tofacitinib in combination with NB-UVB phototherapy may be an effective and safe alternative modality for refractory vitiligo. This article is protected by copyright. All rights reserved.

19.
J Oncol ; 2022: 8943643, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059798

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is, by far, the most prevalent and fatal kind of kidney cancer. Ferrochelatase (FECH) is an enzyme that performs a significant function in the onset and progression of many distinct kinds of malignant tumors. Nevertheless, its predictive usefulness in renal clear cell carcinoma (RCC) has not yet been fully investigated. Methods: FECH expression in ccRCC and healthy adjoining tissues was primarily screened utilizing data sourced from The Cancer Genome Atlas (TCGA) and subsequently validated using data from an independent cohort derived from the Gene Expression Omnibus (GEO) and the Human Protein Atlas HPA databases. The relationship among FECH expression, clinicopathological parameters, and overall survival (OS) was assessed utilizing multivariate analysis and Kaplan-Meier survival curves. Additionally, the protein networks with FECH interaction were constructed with the aid of the online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Gene ontology (GO) analysis, and gene set enrichment analysis (GSEA) were conducted based on TCGA data, and a single-sample GSEA was utilized to explore the link between FECH expression and the infiltration status of immune cells in the tumor. The Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases were utilized to investigate the relationships of FECH expression with the infiltrating immune cells and the matching gene marker sets. Results: FECH expression was shown to be substantially lowered in ccRCC tumors as opposed to that observed in normal tissues (p < 0.05). Lower levels of FECH expression were shown to have a strong association with higher grades of cancer and more advanced TNM stages. The findings of multivariate and univariate analyses illustrated that the OS in patients with ccRCC with low FECH expression is shorter in contrast with that in the high FECH expression group (p < 0.05). It was discovered that CPOX and frataxin are key proteins that interact with FECH. ccRCC with FECH deficiency was linked to the lack of infiltrating immune cells and their respective marker sets, which included CD4+ T cells. Conclusion: In ccRCC, decreased FECH expression was linked to disease progression, unfavorable prognosis, and impaired immune cell infiltration.

20.
Front Genet ; 13: 959684, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061202

RESUMO

This study analyzed PSAT1-targeted miRNAs as a prognostic predictor for gastric cancer. The relationship between the clinical manifestations of gastric cancer in patients and phosphoserine aminotransferase 1 (PSAT1) was analyzed using correlation analysis. PSAT1 was highly expressed in gastric cancer, and its low expression was associated with a poor prognosis. By pan-cancer analysis, PSAT1 could affect the tumor immune microenvironment by immune infiltration analysis. Nine microRNAs targeting PSAT1 and associated with gastric cancer were screened by miRwalk and microRNA expression in TCGA tumor tissues. Six microRNAs were obtained by survival curve analysis, including hsa-miR-1-3p, hsa-miR-139-5p, hsa-miR-145-5p, hsa-miR-195-5p, hsa-miR-218-5p, and hsa-miR-497-5p. Based on the above six microRNAs, a model for bone metastasis prediction in gastric cancer prediction was constructed. An analysis of a decision curve was performed based on the microRNAs obtained to predict bone metastasis from gastric cancer. It had a positive area under the curve (AUC) value of 0.746, and the decision curve analysis (DCA) indicated that it was clinically significant. Dual-luciferase reporter genes indicated that hsa-miR-497-5p and PSAT1 were targeted, and qRT-PCR results confirmed that hsa-miR-497-5p could down-regulate PSAT1 expression. MicroRNAs targeting the regulation of PSAT1 expression can well predict the prognosis of gastric cancer.

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