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1.
Nat Commun ; 15(1): 4881, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849358

RESUMO

N6-methyladenosine (m6A) plays critical roles in regulating mRNA metabolism. However, comprehensive m6A methylomes in different plant tissues with single-base precision have yet to be reported. Here, we present transcriptome-wide m6A maps at single-base resolution in different tissues of rice and Arabidopsis using m6A-SAC-seq. Our analysis uncovers a total of 205,691 m6A sites distributed across 22,574 genes in rice, and 188,282 m6A sites across 19,984 genes in Arabidopsis. The evolutionarily conserved m6A sites in rice and Arabidopsis ortholog gene pairs are involved in controlling tissue development, photosynthesis and stress response. We observe an overall mRNA stabilization effect by 3' UTR m6A sites in certain plant tissues. Like in mammals, a positive correlation between the m6A level and the length of internal exons is also observed in plant mRNA, except for the last exon. Our data suggest an active m6A deposition process occurring near the stop codon in plant mRNA. In addition, the MTA-installed plant mRNA m6A sites correlate with both translation promotion and translation suppression, depicting a more complicated regulatory picture. Our results therefore provide in-depth resources for relating single-base resolution m6A sites with functions in plants and uncover a suppression-activation model controlling m6A biogenesis across species.


Assuntos
Adenosina , Arabidopsis , Regulação da Expressão Gênica de Plantas , Oryza , RNA Mensageiro , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Adenosina/análogos & derivados , Adenosina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Transcriptoma/genética , RNA de Plantas/genética , RNA de Plantas/metabolismo , Regiões 3' não Traduzidas/genética , Perfilação da Expressão Gênica/métodos , Estabilidade de RNA/genética , Éxons/genética , Códon de Terminação/genética
2.
Int J Surg ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905490

RESUMO

OBJECTIVE: The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis. METHODS: We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors. RESULTS: 17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation (HR:5.634, 95%CI:1.663-19.086, P=0.005), Noonan syndrome (HR:3.770, 95%CI:1.245-11.419, P=0.019), preoperational systolic anterior motion (SAM)(HR:4.596, 95%CI:1.532-13.792, P=0.007)and mid-ventricular obstruction (HR:4.763, 95%CI:1.538-14.754, P=0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior (P=0.014), mid-inferoseptal(P=0.044), mid-inferior(P=0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis. CONCLUSION: Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38639281

RESUMO

As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein's clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.

4.
Dig Dis Sci ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662158

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) have been shown to be related to the occurrence and development of a variety of cancers including hepatocellular carcinoma (HCC). However, a large number of potential HCC-related lncRNAs remain undiscovered and are yet to be fully understood. METHODS: Differentially expressed lncRNAs were first obtained from the tumor tissues and adjacent normal tissues of five HCC patients using high-throughput microarray chips. Then the expression levels of 10 differentially expressed lncRNAs were verified in 50 pairs of tissue samples from patients with HCC by quantitative real-time PCR (qRT-PCR). The oncogenic effects of lncRNA-4045 (ENST00000524045.6) in HCC cell lines were verified through a series of in vitro experiments including CCK-8 assay, plate clone formation assay, transwell assay, scratch assay, and flow cytometry. Subsequently, the potential target genes of lncRNA-4045 were predicted by bioinformatics analysis, fluorescence in situ hybridization assay, and RNA sequencing. The mechanism of lncRNA-4045 in HCC was explored by WB assay as well as rescue and enhancement experiments. RESULTS: The results from microarray chips showed 1,708 lncRNAs to have been significantly upregulated and 2725 lncRNAs to have been significantly downregulated in HCC tissues. Via validation in 50 HCC patients, a novel lncRNA lncRNA-4045 was found significantly upregulated in HCC tissues. Additionally, a series of in vitro experiments showed that lncRNA-4045 promoted the proliferation, invasion, and migration of HCC cell lines, and inhibited the apoptosis of HCC cell lines. The results of qRT-PCR in HCC tissues showed that the expression levels of AKR1B10 were significantly positively correlated with lncRNA-4045. LncRNA-4045 knockdown significantly down-regulated AKR1B10 protein expression, and overexpression of lncRNA-4045 led to significant up-regulation of AKR1B10 protein in HCC cell lines. Lastly, down-regulation of AKR1B10 could partially eliminate the enhancement of cell proliferation induced by lncRNA-4045 overexpression, while up-regulation of AKR1B10 was shown to enhance those effects. CONCLUSION: LncRNA-4045 may promote HCC via enhancement of the expression of AKR1B10 protein.

5.
Diabetol Metab Syndr ; 16(1): 64, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38468345

RESUMO

BACKGROUND: Numerous previous studies have reported an association between type 2 diabetes mellitus (T2DM) and lung cancer risk, but the underlying mechanism of the interaction remains unclear. This study aimed to investigate the shared genetic features and immune infiltration processes between lung cancer and T2DM. METHODS: Epidemiological data from the National Health and Nutrition Examination Survey (NHANES) 2000-2018 was used to explore the relationship between lung cancer and diabetes systematically. In addition, we also used bioinformatics methods to analyze the transcriptome data from the Gene Expression Omnibus (GEO) to explore the potential functional mechanisms from the perspective of genes and immune infiltration. RESULTS: Logistic regression analysis showed that prediabetes (OR = 3.289,95%CI 1.231, 8.788, p = 0.01760, model 3)and type 2 diabetes (OR = 3.032 95%CI,1.015, 9.054, p = 0.04689) were significantly associated with an increased risk of lung cancer after adjusting for multiple covariates. Data from NHANES showed an inverted U-shaped relationship between fasting blood glucose and glycosylated haemoglobin and the risk of lung cancer (P for non-linear < 0.001). Transcriptome data showed that we screened 57 co-DEGs, of which 25 were up-regulated co-DEGs and 32 were down-regulated. Ten core DEGs were identified by bioinformatics analysis, which were SMC6, CDC27, CDC7, RACGAP1, SMC4, NCF4, NCF1, NCF2, SELPLG and CFP. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells. CONCLUSION: The identified core genes of NSCLC and T2DM are associated with dysregulated immune cells, which provides a potential research avenue for diagnosing and treating lung cancer combined with diabetes.

6.
Sci Rep ; 14(1): 4801, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413783

RESUMO

An innovative energy-absorbing and bearing structure was proposed, which incorporated the coupling of glass microspheres with a metal tube. Glass microsphere-filled steel tube (GMFST) column, consisting of external steel tube and inner glass microspheres, was expected to give full play to the energy-absorbing and load-bearing capacities of the particle while restricting particle flow from collapsing, thereby enhancing the overall structural strength. Four groups of steel tubes and the GMFST specimens were designed and subjected to axial compression tests at four different loading rates to investigate the performance of the structure. These tests aimed to analyze the deformation mode, mechanical response, and energy absorption capacity of the GMFST columns under quasi-static to low-speed compression conditions. The results indicated that the deformation process and failure mode of GMFST columns were similar to those of hollow steel tubes, albeit with a different post-buckling mode. Filling the steel tubes with glass microspheres reduced the load fluctuation range, moderated load-displacement curves, and exhibited a strain rate strengthening effect. The GMFST columns demonstrated superior energy absorption capacity, with significant increases in crush force efficiency, the averaged crush force, and the total absorbed energy, particularly in terms of subsequent support capacity. The load-increasing reinforcement properties enabled GMFST columns to overcome the limitations associated with the unstable post-buckling path of energy­absorbing damping structure, exhibiting outstanding load-bearing performance and stability in the later stages. The results provided valuable guidelines for designing and engineering high-performance GMFST columns, serving as a new type of energy-absorbing and supporting structure.

7.
Langmuir ; 40(8): 4174-4185, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38359328

RESUMO

Emulsification flooding can effectively enhance crude oil recovery to solve the problem of petroleum shortage. In this work, a modified Janus Nano Calcium carbonate (JNC-12) with a particle size of 30-150 nm was synthesized, and an in situ emulsification nanofluid (ISEN) was prepared with JNC-12 and alkyl polyglycoside (APG). Scanning electron microscope (SEM) showed that the dispersion of JNC-12 in air or APG solution was better than Nano Calcium carbonate (Nano CaCO3). The emulsification properties, interfacial tension, and expansion modulus of ISEN were studied, and the result showed that with the increase in salinity, the emulsification rate decreased, the water yield rate increased, the interfacial tension first decreased and then increased, and the expansion modulus first increased and then decreased. With the increase in temperature, the emulsification rate, emulsion viscosity, and interfacial tension decreased. With the increased oil-water volume, the water yield rate and the emulsion viscosity increased. With increase in the concentration of JNC-12, the water yield rate, the emulsion viscosity, and the interfacial tension decreased but the expansion modulus increased. The emulsion generated by emulsifying ISEN with crude oil was an O/W emulsion, the crude oil viscosity was 4-10 times that of emulsion, and the average particle size of emulsion was 1.107 µm. The addition of ISEN caused the decrease in interfacial tension of oil-water to 0.01-0.1 mN/m. The wettability alteration experiment found that ISEN could change the lipophilic rock to hydrophilic rock. Finally, the core displacement experiments showed that compared with the first water flooding, the oil recovery of the second water flooding after ISEN flooding enhanced by 17.6%. This research has important guiding significance for in situ emulsified nanofluid flooding to enhance oil recovery.

8.
Environ Sci Pollut Res Int ; 31(15): 23077-23090, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416356

RESUMO

The contamination of toxic heavy metals in aquatic environments has garnered significant global attention due to its detrimental effects on marine organisms and human health. Hexavalent chromium is a typical environmental and occupational heavy metal pollutant, identified as carcinogenic heavy metal. This study aimed to assess the impact of different Cr (VI) concentrations (0.05-2.5 mg/L) on Urechis unicinctus (U. unicinctus) by investigating bioaccumulation, antioxidant defense system, expression of resistance-related genes, and histological issues. A clear concentration-effect relationship was observed in the bioaccumulation of Cr (VI) in muscle tissues of U. unicinctus. Moreover, exposure to Cr (VI) can alter the activities of lysozyme (LSZ), catalase (CAT), and superoxide dismutase (SOD) to enhance cellular defense mechanisms in U. unicinctus. Likewise, maintained the normal protein structure and functional stability by regulating protein folding. The heat shock cognitive protein (HSC70) gene showed an upward and then downward trend after Cr (VI) exposure. At 12 h, the HSC70 gene expression reached the maximum values of 4.75 and 4.61-fold in the 0.1 and 1.5 mg/L groups, respectively. The organism produced a large number of free radicals, and elevated level of metallothionein (MT) was used to scavenge free radicals and alleviate oxidative stress. Additionally, histopathological examination revealed disorganization in the midgut, atrophic changes in intestinal connective tissue, uneven distribution in respiratory tissues, and irregular shape with a significant reduction in epithelial cells within the gastric cavity. These findings can serve as a valuable reference for elucidating the toxicity mechanisms of heavy metals towards marine benthic organisms and enhancing water environment monitoring strategies.


Assuntos
Metais Pesados , Poliquetos , Animais , Humanos , Bioacumulação , Cromo/metabolismo , Metais Pesados/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Poliquetos/metabolismo , Radicais Livres
9.
Antiviral Res ; 222: 105797, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38185222

RESUMO

RNA viral infections seriously endanger human health. Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2) suppresses innate immunity against influenza A virus, and pharmacological inhibition of SHP2 provokes hepatic innate immunity. SHP2 binds and catalyzes tyrosyl dephosphorylation of protein zero-related (PZR), but the regulatory effect of PZR on innate immune response to viral infection is unclear. In this study, the transcription and protein level of PZR in host cells were found to be decreased with RNA viral infection, and high level of PZR was uncovered to inhibit interferon (IFN) signaling mediated by RIG-I and MDA5. Through localizing in mitochondria, PZR targeted and interacted with MAVS (also known as IPS-1/VISA/Cardif), suppressing the aggregation and activation of MAVS. Specifically, Y263 residue in ITIM is critical for PZR to exert immunosuppression under RNA viral infection. Moreover, the recruited SHP2 by PZR that modified with tyrosine phosphorylation under RNA viral infection might inhibit phosphorylation activation of MAVS. In conclusion, PZR and SHP2 suppress innate immune response to RNA viral infection through inhibiting MAVS activation. This study reveals the regulatory mechanism of PZR-SHP2-MAVS signal axis on IFN signaling mediated by RIG-I and MDA5, which may provide new sight for developing antiviral drugs.


Assuntos
Infecções por Vírus de RNA , Vírus de RNA , Viroses , Humanos , Transdução de Sinais , Proteína DEAD-box 58 , Imunidade Inata , Interferons , RNA
10.
Front Oncol ; 13: 1255768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074666

RESUMO

Background: Giant (with a diameter of at least 40 mm and a volume of at least 10 cm3) pituitary adenomas (GPAs) are intricate tumors that pose considerable difficulty for surgical removal. While endoscopic transsphenoidal surgery (ETS) is a commonly employed technique for these destructive tumors, its effectiveness may be restricted in cases where invasion into multiple compartments is present, leading to limited resection. Methods: A retrospective review was conducted on the clinical records of 94 patients diagnosed with GPAs who had undergone surgical resection from 2014 to 2022. An analysis was conducted on the outcomes of the surgical and clinical procedures. Results: In this group, the average size of the tumor before surgery was 44.6 ± 5.6 mm (range, 40-73 mm), and the volume was 25. 5± 16.6 cm3 (range, 10-20.67 cm3). Of the total number of patients, 72 (76.6%) underwent a single ETS, 12 (12.8%) opted for transcranial surgery (TCS), and 10 (10.6%) chose a combined method. Gross total resection (GTR) was successfully performed in 49 (68.1%), 3 (25.0%), and 8 (80.0%) patients who underwent each surgical approach. Seventy-four (78.7%) patients had improved vision, 20 (21.3%) were unchanged, and none had deterioration. Twenty-two patients (23.4%) experienced a total of 43 complications, which comprised hormonal insufficiency (11/94, 11.7%), diabetic insipidus (6/88, 6.8%), electrolyte disorders (7/94, 7.4%), cerebrospinal fluid leakage (5/94, 5.3%), meningitis (8/94, 8.5%), and hydrocephalus (6/94, 6.4%). The GTR, subtotal resection (STR), and partial resection (PTR) rates were 63.8% (60/94), 21.3% (20/94), and 14.9% (14/94), respectively. Throughout the follow-up duration, 18.1% (17/94) of patients required reoperation and/or adjuvant radiation treatment as a result of tumor regrowth or inadequate biochemical remission of functioning GPAs. Conclusion: ETS remains the optimal surgical option for most GPAs and generally offers safe and efficient tumor resection. However, a combined approach with TCS remains a requirement in cases that are not suitable for treatment with a single ETS. To achieve optimal tumor removal and minimize the occurrence of surgical complications, a flexible combination of ETS and TCS is recommended based on the characteristics of the tumor.

11.
Biomark Med ; 17(18): 755-765, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-38095985

RESUMO

Background: To explore the biological function and the underlying mechanisms of GOT2 in hepatocellular carcinoma (HCC). Materials & methods: The expression level and prognostic value of GOT2 were examined using International Cancer Genome Consortium and International Cancer Proteogenome Consortium databases. The cell counting kit-8 method, clone formation, Transwell® assays and western blotting were used to evaluate the effects of GOT2 on the biological function and autophagy of HCC cells. Results: The expression of GOT2 was downregulated in HCC tissues and correlated with poor prognosis of HCC patients. Knockdown of GOT2 promoted proliferation, migration and invasion of HCC cells and promoted cells' proliferation by inducing autophagy. Conclusion: GOT2 plays a tumor-inhibitory role in HCC and may be a potential therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Prognóstico
12.
Front Vet Sci ; 10: 1302801, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38144468

RESUMO

The objective of this study was to examine the effects of dietary Chinese herbal medicine (CHM) consisting of Astragalus membranaceus (Fisch.) Bunge (AMT) and Codonopsis pilosula (Franch.) Nannf (CPO) extracts on growth performance, antioxidant capacity, immune status, and intestinal health of broiler chickens. Two groups were formed, each consisting of six replicates of 12 one-day-old healthy male 817 white feather broilers. Broilers were fed either a basal diet (CON group) or a basal diet supplemented with 500 mg/kg CHM. The trial lasted 50 days. The results showed that CHM supplementation resulted in enhanced feed efficiency and antioxidant capacity in both the serum and liver, while it reduced uric acid and endotoxin levels, as well as diamine oxidase activity (p < 0.05). Additionally, CHM treatment increased the height of jejunum villi and upregulated Claudin-1 expression in the jejunal mucosa accompanied by an increase in the mRNA levels of interleukin-6 (IL-6), interferon-γ (IFN-γ), interferon-ß (IFN-ß), tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokine interleukin-10 (IL-10) (p < 0.05). The presence of dietary CHM caused an increase in the proportions of Bacteroidetes and unclassified Bacteroidales but led to a decrease in those of Firmicutes and Alistipes (p < 0.05). The composition of the jejunal mucosa microbiota was correlated with the feed conversion ratio, serum metabolites, and gene expression based on Spearman correlation analysis. The findings indicated that the consumption of dietary CHM improved the utilization of feed, increased the mRNA expression of pro-inflammatory cytokines in the jejunal mucosa, and decreased the endotoxin level and activities of diamine oxidase and lactate dehydrogenase in the serum, which could potentially be linked to changes in the gut microbiota of broiler chickens.

13.
Virol J ; 20(1): 297, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102627

RESUMO

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide with a serious threat to women's health. Persistent infection with high-risk human papillomavirus (HR-HPV) has been identified as the main cause of cervical cancer. This study aimed to evaluate the prevalence and genotype distribution of HR-HPV among women in Jingzhou, Hubei province, China, which is critical for the government to formulate the precision strategies of cervical cancer screening and HPV vaccine innoculation. METHODS: To obtain the baseline data on the population-based prevalence and genotype distribution of HR-HPV infection among age groups and different years, a total of 51,720 women from 2018 to 2022 who went to Jingzhou Hospital Affiliated to Yangtze University for physical examination or gynacological treatment and received HR-HPV DNA genotyping were included in this retrospective study. The possible cervicovaginal infection of 15 high-risk HPV genotypes were analyzed by multiplex fluorescent real-time PCR, including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 82. RESULTS: The overall high-risk HPV prevalence among 51,720 women was 18.75% (9,698/51,720), and the HPV-positive rate of physical examination group (PEG) was 13.22% (541/4,091), which was lower than the HPV-positive rate of gynacological checkup group (GCG) 19.23% (9,157/47,629), with statistical difference (χ2 = 89.069, P < 0.01). The five most common prevalent genotypes were HPV52 (6.55%), HPV58 (3.41%), HPV16 (2.58%), HPV68 (1.82%) and HPV51 (1.57%). Single HPV infection was the predominant (14.36%), which compared to double (3.34%) and multiple (1.05%) infections. The HPV-positive rate was the highest in the > 60 age group (31.73%), and the lowest in the 31-40 age group (15.46%). CONCLUSIONS: The prevalence of high-risk HPV infection among women in Jingzhou area was 18.75%. HPV52, HPV58 and HPV16 genotypes were the most common. The higher prevalence was in the > 60 and ≤ 20 age group, which showed a "U" shape curve, suggesting the necessity of screening among older women to decrease the mortality of cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Idoso , Prevalência , Detecção Precoce de Câncer , Estudos Retrospectivos , Genótipo , China/epidemiologia , Papillomaviridae/genética , Papillomavirus Humano 16/genética
14.
Case Rep Oncol ; 16(1): 652-661, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37900799

RESUMO

Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8-27.1% of patients experiencing a rash of any grade, and 5.2-6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky's sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.

15.
Zhongguo Zhen Jiu ; 43(10): 1123-7, 2023 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-37802517

RESUMO

OBJECTIVE: To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise. METHODS: A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated. RESULTS: After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01). CONCLUSION: Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.


Assuntos
Terapia por Acupuntura , Neoplasias da Mama , Linfedema , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Extremidade Superior , Resultado do Tratamento , Linfedema/etiologia , Linfedema/terapia
16.
Polymers (Basel) ; 15(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37835935

RESUMO

CO2 flooding is a favorable technical means for the efficient development of low-permeability reservoirs, and it can also contribute to the realization of net-zero CO2 emissions. However, due to the unfavorable viscosity ratio and gravity overriding effect, CO2 channeling will inevitably occur, seriously affecting its storage and displacement effects. This paper conducts a systematic study on the application of polymer-assisted CO2 flooding in low-permeability reservoirs. Firstly, the polymer agent suitable for low-permeability reservoirs is optimized through the viscosity-increasing, rheological, and temperature- and salt-resistant properties of the solution. Then, the injectivity performance, resistance-increasing ability, and profile-improving effect of the polymer solution were evaluated through core experiments, and the optimum concentration was optimized. Finally, the enhanced oil recovery (EOR) effects of polymer-assisted and water-assisted CO2 flooding were compared. The results show that the temperature-resistant polymer surfactant (TRPS) has a certain viscosity-increasing performance, good temperature resistance performance, and can react with CO2 to increase the solution viscosity significantly. Meanwhile, TRPS has good injection performance and resistance-increasing effect. The resistance increasing factor (η and η') of TRPS-assisted CO2 flooding increases with increased permeability, the concentration of TRPS solution, and injection rounds. Considering η' and the profile improvement effect comprehensively, the application concentration of TRPS should be 1000 mg/L. The EOR effect of TRPS-assisted CO2 flooding is 8.21% higher than that of water-assisted CO2 flooding. The main effective period is in the first and second rounds, and the best injection round is three. The research content of this paper can provide data support for the field application of polymer-assisted CO2 flooding in low-permeability reservoirs.

17.
MycoKeys ; 98: 1-18, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37287766

RESUMO

Wood-inhabiting fungi are abundant in China, but their distribution is uneven, with more fungi in southwest China and fewer fungi in northwest China. During the investigation of wood-inhabiting fungi in Xinjiang, we collected a large number of specimens. Eight specimens growing on Piceaschrenkiana were collected from Tianshan Mountains, and they were described as two new species in Ceriporiopsis and Sidera based on morphological characters and molecular evidence. Ceriporiopsistianshanensis is characterized by a cream to salmon-buff pore surface, larger pores measuring 1-3 per mm, and broadly ellipsoid basidiospores 5-6.5 × 3-4 µm. Sideratianshanensis is characterized by annual to perennial basidiocarps, measuring 15 mm thick, pores 5-7 per mm, cream to rosy buff pore surface, and allantoid basidiospores 3-3.5 × 1-1.4 µm. Detailed illustrations and descriptions of the novel species are provided.

18.
Mol Cell ; 83(12): 2003-2019.e6, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37257451

RESUMO

Regulation of RNA substrate selectivity of m6A demethylase ALKBH5 remains elusive. Here, we identify RNA-binding motif protein 33 (RBM33) as a previously unrecognized m6A-binding protein that plays a critical role in ALKBH5-mediated mRNA m6A demethylation of a subset of mRNA transcripts by forming a complex with ALKBH5. RBM33 recruits ALKBH5 to its m6A-marked substrate and activates ALKBH5 demethylase activity through the removal of its SUMOylation. We further demonstrate that RBM33 is critical for the tumorigenesis of head-neck squamous cell carcinoma (HNSCC). RBM33 promotes autophagy by recruiting ALKBH5 to demethylate and stabilize DDIT4 mRNA, which is responsible for the oncogenic function of RBM33 in HNSCC cells. Altogether, our study uncovers the mechanism of selectively demethylate m6A methylation of a subset of transcripts during tumorigenesis that may explain demethylation selectivity in other cellular processes, and we showed its importance in the maintenance of tumorigenesis of HNSCC.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Carcinogênese
19.
Eur Radiol ; 33(10): 6781-6793, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37148350

RESUMO

OBJECTIVES: This study evaluated the ability of a preoperative contrast-enhanced CT (CECT)-based radiomics nomogram to differentiate benign and malignant primary retroperitoneal tumors (PRT). METHODS: Images and data from 340 patients with pathologically confirmed PRT were randomly placed into training (n = 239) and validation sets (n = 101). Two radiologists independently analyzed all CT images and made measurements. Key characteristics were identified through least absolute shrinkage selection combined with four machine-learning classifiers (support vector machine, generalized linear model, random forest, and artificial neural network back propagation) to create a radiomics signature. Demographic data and CECT characteristics were analyzed to formulate a clinico-radiological model. Independent clinical variables were merged with the best-performing radiomics signature to develop a radiomics nomogram. The discrimination capacity and clinical value of three models were quantified by the area under the receiver operating characteristics (AUC), accuracy, and decision curve analysis. RESULTS: The radiomics nomogram was able to consistently differentiate between benign and malignant PRT in the training and validation datasets, with AUCs of 0.923 and 0.907, respectively. Decision curve analysis manifested that the nomogram achieved higher clinical net benefits than did separate use of the radiomics signature and clinico-radiological model. CONCLUSIONS: The preoperative nomogram is valuable for differentiating between benign and malignant PRT; it can also aid in treatment planning. KEY POINTS: • A noninvasive and accurate preoperative determination of benign and malignant PRT is crucial to identifying suitable treatments and predicting disease prognosis. • Associating the radiomics signature with clinical factors facilitates differentiation of malignant from benign PRT with improved diagnostic efficacy (AUC) and accuracy from 0.772 to 0.907 and from 0.723 to 0.842, respectively, compared with the clinico-radiological model alone. • For some PRT with anatomically special locations and when biopsy is extremely difficult and risky, a radiomics nomogram may provide a promising preoperative alternative for distinguishing benignity and malignancy.


Assuntos
Radiologia , Neoplasias Retroperitoneais , Humanos , Neoplasias Retroperitoneais/diagnóstico por imagem , Nomogramas , Área Sob a Curva , Tomografia Computadorizada por Raios X , Estudos Retrospectivos
20.
Cell Death Dis ; 14(4): 245, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024465

RESUMO

CMTR1, also called IFN-stimulated gene 95 kDa protein (ISG95), is elevated by viral infection in a variety of cells. However, the functions of CMTR1 in colorectal cancer (CRC), especially its roles in tumorigenesis and immune regulation, remain unclear. Here, we first identified CMTR1 as a novel oncogene in colorectal cancer. Based on The Cancer Genome Atlas (TCGA) database exploration and human tissue microarray (TMA) analysis, we found that CMTR1 expression was markedly higher in CRC tissues than in adjacent normal tissues. High CMTR1 expression was correlated with poor prognosis in CRC patients. Knockdown (KD) of CMTR1 significantly suppressed cell proliferation and tumorigenicity both in vitro and in vivo, whereas overexpression of CMTR1 resulted in the opposite effects. KEGG pathway analysis revealed differential enrichment in the JAK/STAT signaling pathway in colorectal cancer cells with CMTR1 KD. Mechanistically, suppression of CMTR1 expression inhibited RNAPII recruitment to the transcription start site (TSS) of STAT3 and suppressed STAT3 expression and activation. Furthermore, the efficacy of PD1 blockade immunotherapy was prominently enhanced in the presence of CMTR1 KD via increased infiltration of CD8 + T cells into the tumor microenvironment. Overall, it appears that CMTR1 plays a key role in regulating tumor cell proliferation and antitumor immunity.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Evasão da Resposta Imune , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Microambiente Tumoral
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