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1.
Plant Biotechnol J ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600703

RESUMEN

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

2.
Nano Lett ; 23(17): 8013-8021, 2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37615624

RESUMEN

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.


Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Yoduro de Potasio/farmacología , Yoduro de Potasio/uso terapéutico , Caolín , Endocitosis , Sistemas de Liberación de Medicamentos , Neoplasias de la Tiroides/tratamiento farmacológico
3.
J Transl Med ; 21(1): 735, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853445

RESUMEN

Although the incidence of thyroid cancer is increasing year by year, most patients, especially those with differentiated thyroid cancer, can usually be cured with surgery, radioactive iodine, and thyroid-stimulating hormone suppression. However, treatment options for patients with poorly differentiated thyroid cancers or radioiodine-refractory thyroid cancer have historically been limited. Altered energy metabolism is one of the hallmarks of cancer and a well-documented feature in thyroid cancer. In a hypoxic environment with extreme nutrient deficiencies resulting from uncontrolled growth, thyroid cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. This review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in thyroid cancer cells, which we expect will yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.


Asunto(s)
Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/patología , Radioisótopos de Yodo/efectos adversos , Adenocarcinoma/tratamiento farmacológico , Glucosa
4.
BMC Musculoskelet Disord ; 24(1): 941, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053090

RESUMEN

BACKGROUND: Cortical buttress are important factors for postoperative stable reconstruction of per/inter-trochanteric fractures. The study aimed to measure the remnant axial cortical length (RACL) of the proximal circumference of the femur, and to determine which part of the RACL can be used reliably to postoperatively sustain the head-neck fragment as a cortical support pattern. METHODS: Eighty patients with trochanteric hip fractures admitted from January 2015 to January 2016 were included in a retrospective study. Their pre-operative computed tomography (CT) images were used to form 3D-CT reconstructions via Mimics software. After simulated rotation and movement for fracture reduction, the RACL, its three component parts-namely, the remnant anterior cortex (RAC), remnant lateral cortex (RLC), and remnant posterior cortex (RPC) -the γ angle between the anterior and posterior cortex, and the Hsu's lateral wall thickness (LWT) were evaluated. RESULTS: Patients with an A1 fracture (21/80) had a longer RACL (88.8 ± 15.8 mm) than those with an A2 fracture (60.0 ± 11.9 mm; P < 0.01). The RAC, RLC, and RPC of the RACL in A1 fractures were also significantly longer than those in A2 fractures (P < 0.001). However, the most significant difference among the three components of the RACL was in the RPC, which was 27.3 ± 7.8 mm in A1 fractures and 9.2 ± 6.6 mm in A2 fractures. In addition, the coefficient of variation of the RAC was only 20.0%, while that of the RPC was 75.5%. The average γ angle in A1 fractures was 16.2 ± 13.1°, which was significantly smaller than that in A2 fractures, which was 40.3 ± 14.5° (P < 0.001). There was a significant statistical difference in the LWT between A1 and A2 fractures (P < 0.001). There were significant differences in the RACL, RAC, RLC, RPC, γ angle, and LWT among the five subtypes (P < 0.001). CONCLUSIONS: The RAC is relatively stable in pertrochanteric fractures. Fracture reduction through a RAC buttress may help to enhance the postoperative stable reconstruction of per/inter-trochanteric fractures and make possible good mechanical support for fracture healing.


Asunto(s)
Fracturas del Fémur , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Fracturas del Fémur/cirugía , Fémur/cirugía , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Tomografía Computarizada por Rayos X/métodos
5.
BMC Musculoskelet Disord ; 24(1): 156, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36855090

RESUMEN

OBJECTIVE: Excessive postoperative sliding is a common complication of intramedullary nails in the treatment of intertrochanteric femur fractures. The aim of this study was to identify risk factors for excessive postoperative sliding in the intertrochanteric fractures treated with an intramedullary nail. METHODS: A retrospective analysis of 369 patients with femoral intertrochanteric fractures treated with short intramedullary nails between February 2017 and September 2020 was performed. Patients were classified into an excessive sliding group (ES group) and a control group according to the sliding distance after 6 months of follow-up. The proximal medullary filling degree (MFD), fracture reduction patterns in the anteroposterior (AP) view and lateral view, and tip-apex distance (TAD) were evaluated and compared in each group. RESULTS: Thirty-three cases were included in the ES group, and 336 cases were included in the control group. No significant differences in age, sex, fracture side, AO Foundation and Orthopaedic Trauma Association (AO/OTA) classification, Dorr classification, Singh Osteoporosis Index (SOI), American Society of Anesthesiologists classification (ASA), TAD or fracture reduction patterns in the AP view were noted between the two groups. The negative reduction pattern can strongly predict excessive postoperative sliding (OR 4.286, 95% CI 1.637-11.216, P = 0.003). The incidence of excessive postoperative sliding increased by 8.713-fold when the MFD decreased by 10% (OR 8.713, 95% CI 1.925-39.437, P = 0.005). CONCLUSIONS: A low medullary filling degree and negative fracture reduction pattern in the lateral view were both independent risk factors for excessive postoperative sliding.


Asunto(s)
Fracturas del Fémur , Fracturas de Cadera , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , Fémur
6.
Int Orthop ; 47(7): 1827-1836, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36976332

RESUMEN

PURPOSE: The purpose of this study is to determine whether the integrity of the entry portal of head-neck implant is related to postoperative mechanical complications. METHODS: We retrospectively reviewed consecutive patients with pertrochanteric fractures in our hospital treated from January 1, 2018, to September 1, 2021. Based on the integrity of the entry portal for head-neck implants on the femoral lateral wall, patients were divided into two groups, including the ruptured entry portal (REP) group and the intact entry portal (IEP) group. After 4:1 propensity score-matched analyses were used to balance the baseline of the two groups, a total of 55 patients were extracted from the original participants, including 11 patients in the REP group and 44 matched patients in the IEP group. The anterior to posterior cortex width on the mid-level of the lesser trochanter was measured and defined as the residual lateral wall width (RLWW). RESULTS: Compared with the IEP group, the REP group was correlated with postoperative mechanical complications (OR = 12.00, 95% CI 1.837-78.369, P = 0.002) and hip-thigh pain (OR = 26.67, 95% CI 4.98-142.86). RLWW ≤ 18.55 mm indicated a high likelihood (tau-y = 0.583, P = 0.000) of becoming the REP type postoperatively and being more likely to suffer from mechanical complications (OR = 30.67, 95% CI 3.91-240.70, P = 0.000) and hip-thigh pain (OR = 14.64, 95% CI 2.36-90.85, P = 0.001). CONCLUSION: Rupture of entry portal is a high-risk factor for mechanical complications in intertrochanteric fractures. RLWW ≤ 18.55 mm is a reliable predictor of the postoperative REP type.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Fijación Intramedular de Fracturas/efectos adversos , Fracturas de Cadera/cirugía , Fracturas de Cadera/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Dolor/etiología , Clavos Ortopédicos/efectos adversos , Resultado del Tratamiento
7.
Int J Mol Sci ; 24(6)2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36983005

RESUMEN

Immune modulation is a critical factor in determining the survival of patients with malignancies, including those with oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). Immune escape or stimulation may be driven by the B7/CD28 family and other checkpoint molecules, forming ligand-receptor complexes with immune cells in the tumor microenvironment. Since the members of B7/CD28 can functionally compensate for or counteract each other, the concomitant disruption of multiple members of B7/CD28 in OSCC or HNSCC pathogenesis remains elusive. Transcriptome analysis was performed on 54 OSCC tumors and 28 paired normal oral tissue samples. Upregulation of CD80, CD86, PD-L1, PD-L2, CD276, VTCN1, and CTLA4 and downregulation of L-ICOS in OSCC relative to the control were noted. Concordance in the expression of CD80, CD86, PD-L1, PD-L2, and L-ICOS with CD28 members was observed across tumors. Lower ICOS expression indicated a worse prognosis in late-stage tumors. Moreover, tumors harboring higher PD-L1/ICOS, PD-L2/ICOS, or CD276/ICOS expression ratios had a worse prognosis. The survival of node-positive patients was further worsened in tumors exhibiting higher ratios between PD-L1, PD-L2, or CD276 and ICOS. Alterations in T cell, macrophage, myeloid dendritic cell, and mast cell populations in tumors relative to controls were found. Decreased memory B cells, CD8+ T cells, and Tregs, together with increased resting NK cells and M0 macrophages, occurred in tumors with a worse prognosis. This study confirmed frequent upregulation and eminent co-disruption of B7/CD28 members in OSCC tumors. The ratio between PD-L2 and ICOS is a promising survival predictor in node-positive HNSCC patients.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Antígenos CD28 , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Carcinoma de Células Escamosas/patología , Linfocitos T CD8-positivos/metabolismo , Neoplasias de la Boca/patología , Antígeno B7-1/metabolismo , Moléculas de Adhesión Celular , Factores Inmunológicos , Microambiente Tumoral , Antígenos B7/genética
8.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4693-4701, 2023 Sep.
Artículo en Zh | MEDLINE | ID: mdl-37802808

RESUMEN

This study aimed to examine the effect and underlying mechanism of Puerariae Lobatae Radix on insulin resistance in db/db mice with type 2 diabetes mellitus(T2DM) based on the analysis of intestinal flora. Fifty db/db mice were randomly divided into a model group(M group), a metformin group(YX group), a high-dose Puerariae Lobatae Radix group(YGG group), a medium-dose Puerariae Lobatae Radix group(YGZ group), and a low-dose Puerariae Lobatae Radix group(YGD group). Another 10 db/m mice were assigned to the normal group(K group). After continuous administration for eight weeks, body weight and blood sugar of mice were measured. Enzyme linked immunosorbent assay(ELISA) was used to detect glycosylated serum protein(GSP) and fasting serum insulin(FINS), and insulin resistance index(HOMA-IR) was calculated. The histopathological changes in the pancreas were observed by HE staining. Tumor necrosis factor(TNF)-α expression in the pancreas was detected using immunohistochemistry. The structural changes in fecal intestinal flora in the K, M, and YGZ groups were detected by 16S rRNA. Western blot was used to detect the expression of farnesoid X receptor(FXR) and takeda G protein-coupled receptor 5(TGR5) in the ileum, cholesterol 7α-hydroxylase(CYP7A1) and sterol 27α-hydroxylase(CYP27A1) in the liver, and G protein-coupled receptors 41(GPR41) and 43(GPR43) in the colon. Compared with the K group, the M group showed increased body weight, blood sugar, serum GSP, fasting blood glucose(FBG), and FINS, increased HOMA-IR, inflammatory infiltration of islet cells, necrosis and degeneration of massive acinar cells, unclear boundary between islet cells and acinar cells, disturbed intestinal flora, and down-regulated FXR, TGR5, CYP7A1, CYP27A1, GPR41, and GPR43. Compared with the M group, the YX, YGG, YGZ, and YGD groups showed decreased body weight, blood sugar, serum GSP, FBG, and FINS, islet cells with intact and clumpy morphology and clear boundary, necrosis of a few acinar cells, and more visible islet cells. The intestinal flora in the YGZ group changed from phylum to genus levels, and the relative abundance of intestinal flora affecting the metabolites of intestinal flora increased. The protein expression of FXR, TGR5, CYP7A1, CYP27A1, GPR41, and GPR43 increased. The results show that Puerariae Lobatae Radix can improve the inflammatory damage of pancreatic islet cells and reduce insulin resistance in db/db mice with T2DM. The mechanism of action may be related to the increase in the abundance of Actinobacteria, Bifidobacterium, and Bacteroides in the intestinal tract and the protein expression related to metabolites of intestinal flora.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistencia a la Insulina , Pueraria , Ratones , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Pueraria/química , ARN Ribosómico 16S , Peso Corporal , Necrosis
9.
Mol Microbiol ; 116(1): 168-183, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33567149

RESUMEN

Enterohemorrhagic Escherichia coli (EHEC), an enteropathogen that colonizes in the intestine, causes severe diarrhea and hemorrhagic colitis in humans by the expression of the type III secretion system (T3SS) and Shiga-like toxins (Stxs). However, how EHEC can sense and respond to the changes in the alimentary tract and coordinate the expression of these virulence genes remains elusive. The T3SS-related genes are known to be regulated by the locus of enterocyte effacement (LEE)-encoded regulators, such as Ler, as well as non-LEE-encoded regulators in response to different environmental cues. Herein, we report that OmpR, which participates in the adaptation of E. coli to osmolarity and pH alterations, is required for EHEC infection in Caenorhabditis elegans. OmpR protein was able to directly bind to the promoters of ler and stx1 (Shiga-like toxin 1) and regulate the expression of T3SS and Stx1, respectively, at the transcriptional level. Moreover, we demonstrated that the expression of ler in EHEC is in response to the intestinal environment and is regulated by OmpR in C. elegans. Taken together, we reveal that OmpR is an important regulator of EHEC which coordinates the expression of virulence factors during gastrointestinal infection in vivo.


Asunto(s)
Proteínas Bacterianas/genética , Caenorhabditis elegans/microbiología , Escherichia coli Enterohemorrágica/patogenicidad , Toxina Shiga I/biosíntesis , Transactivadores/genética , Factores de Virulencia/biosíntesis , Animales , Proteínas Bacterianas/metabolismo , Sistema Digestivo/microbiología , Escherichia coli Enterohemorrágica/genética , Proteínas de Escherichia coli/biosíntesis , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/genética , Regiones Promotoras Genéticas/genética , Toxina Shiga I/genética , Transactivadores/biosíntesis , Transactivadores/metabolismo , Transcripción Genética/genética , Activación Transcripcional/genética , Sistemas de Secreción Tipo III/biosíntesis , Sistemas de Secreción Tipo III/genética , Factores de Virulencia/genética
10.
Environ Health ; 21(1): 65, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35799180

RESUMEN

BACKGROUND: Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear. METHODS: This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants' residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors. RESULTS: In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3-8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels. CONCLUSIONS: High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.


Asunto(s)
Contaminación del Aire , Exposición a Riesgos Ambientales , Ozono , Nódulo Tiroideo , Adulto , Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Masculino , Ozono/efectos adversos , Material Particulado/análisis , Estudios Retrospectivos , Nódulo Tiroideo/inducido químicamente , Nódulo Tiroideo/epidemiología , Tirotropina
11.
BMC Musculoskelet Disord ; 23(1): 721, 2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-35902901

RESUMEN

We appreciate the interest by Drs. Hagiyama and coauthors in our work entitled "Calcar fracture gapping: a reliable predictor of anteromedial cortical support failure after cephalomedullary nailing for pertrochanteric femur fractures". They discussed several pertinent points and it is our pleasure to respond their concerns in order. Firstly, we agree that calcar fracture gap and anteromedial cortical support are different concepts, though both of them were used to evaluate the displacement of fracture reduction quality. Secondly, our primary outcome parameter was the threshold distance of calcar fracture gapping in anteroposterior and lateral fluoroscopies, which was calculated based on sensitivity and specificity by receiver operating characteristic curves. Thirdly, we took immediate post-operative fluoroscopic images in 3 views to describe the initial reduction quality as baseline to compare and calculate the changes with three-dimensional computed tomography, which was taken about one week after operation for confirming secondary stability after head-neck sliding and impaction. Lastly, the parameters selected in multivariable analysis. Future work with better study-design is needed to improve the prediction of patient outcomes.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas de Cadera , Clavos Ortopédicos , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fémur/cirugía , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Humanos , Estudios Retrospectivos
12.
BMC Musculoskelet Disord ; 23(1): 175, 2022 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-35209887

RESUMEN

BACKGROUND: Maintaining anteromedial cortical support is essential for controlling sliding and decreasing postoperative implant-related complications. However, adequate fracture reduction with cortical support in immediate postoperative fluoroscopy is not invariable in postoperative follow-ups. This study was conducted to investigate the risk factors leading to anteromedial cortical support failure in follow up for pertrochanteric femur fractures treated with cephalomedullary nails. METHODS: This retrospective study enrolled 159 patients with pertrochanteric fractures (AO/OTA- 31A1 and 31A2) that fixed with cephalomedullary nails. All patients were evaluated as adequate fracture reduction in immediate postoperative fluoroscopy before leaving the operation theater. The patients were separated into two groups based on the condition of the anteromedial cortex in the postoperative 3D CT with full-range observation: those with calcar support maintained in Group 1 and those with calcar support lost in Group 2. Demographic information, fracture classification, TAD (tip-apex distance), Cal-TAD, Parker ratio, NSA (neck-shaft angle), reduction quality score, and calcar fracture gapping were collected and compared. Logistic regression analysis was conducted to explore the risk factors leading to anteromedial cortex change. RESULTS: Anteromedial cortical support failure was noted in 46 cases (29%). There was no significant difference between the two groups concerning age, sex, side injury, TAD, Cal-TAD, Parker ratio, or NSA. There was a significant difference in the AO/OTA fracture classification in univariate analysis but no difference in the multivariable analysis. The reduction quality score, calcar fracture gapping in the AP (anteroposterior), and lateral views were significantly associated with anteromedial cortical support failure in follow-up after cephalomedullary nailing in the multivariable analysis. The threshold value of calcar fracture gapping for the risk of loss was 4.2 mm in the AP and 3.8 mm in the lateral fluoroscopies. Mechanical complications (lateral sliding and varus) were frequently observed in the negative anteromedial cortical support group. CONCLUSIONS: Good reduction quality was a protective factor, and larger calcar fracture gapping in the AP and lateral views were risk factors leading to the postoperative loss of anteromedial cortical support. Therefore, we should pay close attention to fracture reduction and minimize the calcar fracture gap during surgery.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Clavos Ortopédicos/efectos adversos , Fémur/cirugía , Fijación Intramedular de Fracturas/efectos adversos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/etiología , Fracturas de Cadera/cirugía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
13.
Int J Mol Sci ; 24(1)2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36614054

RESUMEN

Altered metabolism is a hallmark of aging. The tricarboxylic acid cycle (TCA cycle) is an essential metabolic pathway and plays an important role in lifespan regulation. Supplementation of α-ketoglutarate, a metabolite converted by isocitrate dehydrogenase alpha-1 (idha-1) in the TCA cycle, increases lifespan in C. elegans. However, whether idha-1 can regulate lifespan in C. elegans remains unknown. Here, we reported that the expression of idha-1 modulates lifespan and oxidative stress tolerance in C. elegans. Transgenic overexpression of idha-1 extends lifespan, increases the levels of NADPH/NADP+ ratio, and elevates the tolerance to oxidative stress. Conversely, RNAi knockdown of idha-1 exhibits the opposite effects. In addition, the longevity of eat-2 (ad1116) mutant via dietary restriction (DR) was reduced by idha-1 knockdown, indicating that idha-1 may play a role in DR-mediated longevity. Furthermore, idha-1 mediated lifespan may depend on the target of rapamycin (TOR) signaling. Moreover, the phosphorylation levels of S6 kinase (p-S6K) inversely correlate with idha-1 expression, supporting that the idha-1-mediated lifespan regulation may involve the TOR signaling pathway. Together, our data provide new insights into the understanding of idha-1 new function in lifespan regulation probably via DR and TOR signaling and in oxidative stress tolerance in C. elegans.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Isocitrato Deshidrogenasa , Longevidad , Estrés Oxidativo , Animales , Caenorhabditis elegans/enzimología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Longevidad/genética
14.
Ann Plast Surg ; 87(4): 451-456, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33587459

RESUMEN

BACKGROUND: Dynamic infrared thermography provides a new imaging method of perforator detection. This study introduces an augmented technique to improve its accuracy by tourniquet-reperfusion and reports its preliminary use in the distal lower leg reconstruction. METHODS: A tourniquet (450 mm Hg) was applied for 3 minutes on proximal thighs. After the tourniquet release, the rewarming rate and pattern of hotspots were observed by thermography to delineate the location and quality of perforators. The results were compared with those detected by computed tomographic angiography. Clinically, the local transferred posterior tibial artery or peroneal artery propeller perforator flap was performed in 9 patients for the distal lower leg reconstruction. RESULTS: There was a 20- to 140-second "perforator observing window" after the tourniquet release. Tourniquet-reperfusion augmented thermal imaging method (TRATIM) had a sensitivity of 90.3% and a positive predictive value of 93.3%. The TRATIM and computed tomographic angiography had an excellent concordance with a kappa index value of 0.839 (P < 0.001). Based on the TRATIM, 9 propeller perforator flaps were successfully designed and raised for the distal lower leg resurfacing. All flaps survived entirely, except one with size of 1.0 cm × 2.0 cm that had terminal necrosis. CONCLUSIONS: The TRATIM is a quick, easy, cheap, and reliable approach for perforator detection in the lower leg. With the aid of TRATIM, a customized propeller perforator flap could be raised efficiently for the distal lower leg reconstruction.


Asunto(s)
Colgajo Perforante , Procedimientos de Cirugía Plástica , Humanos , Pierna/cirugía , Reperfusión , Termografía , Torniquetes
15.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34445087

RESUMEN

The miR-31 host gene (MIR31HG) encodes a long non-coding RNA (LncRNA) that harbors miR-31 in its intron 2; miR-31 promotes malignant neoplastic progression. Overexpression of MIR31HG and of miR-31 occurs during oral squamous cell carcinoma (OSCC). However, the downstream effectors modulated by MIR31HG during OSCC pathogenesis remain unclear. The present study identifies up-regulation of MIR31HG expression during the potentially premalignant disorder stage of oral carcinogenesis. The potential of MIR31HG to enhance oncogenicity and to activate Wnt and FAK was identified when there was exogenous MIR31HG expression in OSCC cells. Furthermore, OSCC cell subclones with MIR31HG deleted were established using a Crispr/Cas9 strategy. RNA sequencing data obtained from cells expressing MIR31HG, cells with MIR31HG deleted and cells with miR-31 deleted identified 17 candidate genes that seem to be modulated by MIR31HG in OSCC cells. A TCGA database algorithm pinpointed MMP1, BMP2 and Limb-Bud and Heart development (LBH) as effector genes controlled by MIR31HG during OSCC. Exogenous LBH expression decreases tumor cell invasiveness, while knockdown of LBH reverses the oncogenic suppression present in MIR31HG deletion subclones. The study provides novel insights demonstrating the contribution of the MIR31HG-LBH cascade to oral carcinogenesis.


Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/genética , ARN Largo no Codificante/genética , Factores de Transcripción/genética , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Humanos , Neoplasias de la Boca/patología , Regulación hacia Arriba
16.
Chin J Traumatol ; 24(1): 11-17, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33246880

RESUMEN

PURPOSE: To evaluate the outcomes with and without aid of a computer-assisted surgical navigation system (CASNS) for treatment of unilateral orbital wall fracture (OWF). METHODS: Patients who came to our hospital for repairing unilateral traumatic OWF from 2014 to 2017 were included in this study. The patients were divided into the navigation group who accepted orbital wall reconstruction aided by CASNS and the conventional group. We evaluated the surgical precision in the navigation group by analyzing the difference between actual postoperative computed tomography data and preoperative virtual surgical plan through color order ratios. We also compared the duration of surgery, enophthalmos correction, restoration of orbital volumes, and improvement of clinical symptoms in both groups systemically. Quantitative data were presented as mean ± SD. Significance was determined by the two-sample t-test using SPSS Version 19.0 A p < 0.05 was considered statistically significant. RESULTS: Seventy patients with unilateral OWF were included in the study cohort. The mean difference between preoperative virtual planning and actual reconstruction outcome was (0.869 ± 0.472) mm, which means the reconstruction result could match the navigation planning accurately. The mean duration of surgery in the navigation group was shorter than it is in the control group, but not significantly. Discrepancies between the reconstructed and unaffected orbital-cavity volume and eyeball projection in the navigation group were significantly less than that in the conventional group. One patient had remnant diplopia and two patients had enophthalmos after surgery in the navigation group; two patients had postoperative diplopia and four patients had postoperative enophthalmos in the conventional group. CONCLUSION: Compare with the conventional treatment for OWF, the use of CASNS can provide a significantly better surgical precision, greater improvements in orbital-cavity volume and eyeball projection, and better clinical results, without increasing the duration of surgery.


Asunto(s)
Órbita/cirugía , Fracturas Orbitales/cirugía , Procedimientos de Cirugía Plástica/métodos , Cirugía Asistida por Computador/métodos , Adolescente , Adulto , Diplopía/epidemiología , Enoftalmia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Tempo Operativo , Órbita/patología , Fracturas Orbitales/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
17.
J Biomed Sci ; 27(1): 14, 2020 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-31900139

RESUMEN

BACKGROUND: Extraintestinal pathogenic E. coli (ExPEC) remains one of the most prevalent bacterial pathogens that cause extraintestinal infections, including neonatal meningitis, septicemia, and urinary tract (UT) infections (UTIs). Antibiotic therapy has been the conventional treatment for such infections, but its efficacy has decreased due to the emergence of antibiotic-resistant bacteria. Identification and characterization of bacterial factors that contribute to the severity of infection would facilitate the development of novel therapeutic strategies. The ExPEC periplasmic protease Prc contributes to the pathogen's ability to evade complement-mediated killing in the serum. Here, we further investigated the role of the Prc protease in ExPEC-induced UTIs and the underlying mechanism. METHODS: The uropathogenic role of Prc was determined in a mouse model of UTIs. Using global quantitative proteomic analyses, we revealed that the expression of FliC and other outer membrane-associated proteins was altered by Prc deficiency. Comparative transcriptome analyses identified that Prc deficiency affected expression of the flagellar regulon and genes that are regulated by five extracytoplasmic signaling systems. RESULTS: A mutant ExPEC with a prc deletion was attenuated in bladder and kidney colonization. Global quantitative proteomic analyses of the prc mutant and wild-type ExPEC strains revealed significantly reduced flagellum expression in the absence of Prc, consequently impairing bacterial motility. The prc deletion triggered downregulation of the flhDC operon encoding the master transcriptional regulator of flagellum biogenesis. Overexpressing flhDC restored the prc mutant's motility and ability to colonize the UT, suggesting that the impaired motility is responsible for attenuated UT colonization of the mutant. Further comparative transcriptome analyses revealed that Prc deficiency activated the σE and RcsCDB signaling pathways. These pathways were responsible for the diminished flhDC expression. Finally, the activation of the RcsCDB system was attributed to the intracellular accumulation of a known Prc substrate Spr in the prc mutant. Spr is a peptidoglycan hydrolase and its accumulation destabilizes the bacterial envelope. CONCLUSIONS: We demonstrated for the first time that Prc is essential for full ExPEC virulence in UTIs. Our results collectively support the idea that Prc is essential for bacterial envelope integrity, thus explaining how Prc deficiency results in an attenuated ExPEC.


Asunto(s)
Endopeptidasas/genética , Infecciones por Escherichia coli/genética , Proteínas de Escherichia coli/genética , Escherichia coli Patógena Extraintestinal/genética , Flagelina/genética , Infecciones Urinarias/genética , Animales , Farmacorresistencia Bacteriana/genética , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/patología , Escherichia coli Patógena Extraintestinal/patogenicidad , Regulación Bacteriana de la Expresión Génica/genética , Humanos , Ratones , Proteómica , Transducción de Señal/genética , Infecciones Urinarias/microbiología , Infecciones Urinarias/patología , Escherichia coli Uropatógena/genética , Escherichia coli Uropatógena/patogenicidad , Factores de Virulencia/genética
18.
Soc Psychiatry Psychiatr Epidemiol ; 55(1): 33-43, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31456029

RESUMEN

BACKGROUND AND AIM: Migraine is a highly prevalent and disabling neurological disorder associated with a wide range of psychiatric comorbidities. Studies have revealed that those with migraine headache and coexisting psychiatric disorders have poorer treatment outcomes and increased disability. The study aims to establish the prevalence, correlates, and comorbidities of migraine headache among the multi-ethnic Asian population in Singapore. METHOD: Data were extracted from the Singapore Mental Health Study 2016 (SMHS 2016), a cross-sectional epidemiological survey of a nationally representative sample. Face-to-face interviews were completed with 6126 participants between 2016 and 2017. The data relating to chronic medical conditions, psychiatric conditions, and 30-day functioning and disability were captured using the World Mental Health Composite International Diagnostic Interview (CIDI) version 3.0. RESULTS: The lifetime prevalence for migraine headache in the Singapore general population was 8.2%. Malay ethnicity (versus Chinese), female gender (versus male), and diploma holders (versus university) were significantly more likely to experience migraine headache. Participants belonging to the older age group (65 years and above versus 18-34 years of age), and those who were economically inactive (versus employed) were less likely to experience migraine headache. The mean age of onset for migraine was 26.4 years (SD = 11.1). Poisson regression analyses showed that migraine headache was also significantly associated with psychiatric conditions such as major depressive disorder (MDD) (prevalence ratio (PR), 1.80; 95% CI, 1.25-2.58), bipolar disorder (BD) (PR, 3.55; 95% CI, 2.29-5.51), generalized anxiety disorder (GAD) (PR, 2.04; 95% CI, 1.12-3.69), obsessive compulsive disorder (OCD) (PR, 2.20; 95% CI, 1.49-3.26), and alcohol use disorder (AUD) (PR, 1.93; 95% CI, 1.20-3.08). Those with migraine headache were significantly associated with poor functioning and disability compared to those without migraine headache. CONCLUSIONS AND DISCUSSION: Our study showed significant associations between migraine headache and psychiatric disorders, as well as with role functioning and disability. The findings of our study emphasise the need for screening for psychiatric comorbidity among those with migraine and the development of appropriate interventions for this group.


Asunto(s)
Trastornos Mentales/epidemiología , Trastornos Migrañosos/epidemiología , Adolescente , Adulto , Anciano , Alcoholismo/epidemiología , Trastornos de Ansiedad/epidemiología , Trastorno Bipolar/epidemiología , Enfermedad Crónica , Comorbilidad , Estudios Transversales , Trastorno Depresivo Mayor/epidemiología , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Trastornos Mentales/etnología , Persona de Mediana Edad , Trastornos Migrañosos/etnología , Trastorno Obsesivo Compulsivo/epidemiología , Distribución de Poisson , Prevalencia , Singapur/epidemiología , Adulto Joven
19.
BMC Musculoskelet Disord ; 21(1): 719, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33153440

RESUMEN

BACKGROUND: Anteromedial cortex-to-cortex reduction is a key parameter for stable reconstruction of the fracture fragments during the intertrochanteric fracture fixation. This paper introduces the oblique fluoroscopic projection as a novel method to evaluate the quality of anteromedial cortical apposition. METHODS: Three proximal femur specimens were marked with steel wires along five anatomic landmarks: Greater trochanter, Lesser trochanter, Intertrochanteric line, Anterolateral tubercle and the Anteromedial cortical line. After obtaining the standard femoral neck AP and lateral fluoroscopic images, the C-arm was rotated by every 5°increments until a clear tangential view of the antero-medial-inferior corner cortex was observed. 98 cases of intertrochanteric hip fractures were enrolled from April 2018 to October 2019. After fixation with the nails, the intra-operative anteromedial cortex reduction quality was evaluated from the AP, the true lateral, and the new anteromedial oblique fluoroscopic images. The fluoroscopic results were compared with the post-operative 3D-CT reconstruction images. RESULTS: The specimen study showed that internal rotation of the C-arm to approximately 30 ° can remove all the obscure shadows and clearly display the antero-medial-inferior cortical tangent line. Clinically,the positive, neutral and negative apposition of different cortices via intra-operative fluoroscopic images showed79, 19 and 0 cases of medial cortical apposition in AP views; 2, 68 and 28 cases of anterior cortices in lateral views;and 22, 51 and 25cases of anteromedial cortical apposition in oblique views respectively. The post-operative 3D-CT reconstruction images revealed that the final anteromedial cortical contact was noted in 62 cases (63.3%), and lost in 36 cases (36.7%). The overall coincidence rate between intra-operative fluoroscopy and post-operative 3D-CT was 63.3% (62/98) in AP view,79.6% (78/98) in lateral view, and 86.7% (85/98) in oblique view(p < 0.001). Negative cortical apposition in oblique view was highly predictive of a final loss of cortical support on 3D CT (24/25 cases, 96%).And non-negative cortical apposition in oblique view was highly associated with true cortical support on 3D CT images (61/73 cases, 83.6%) (p < 0.001). CONCLUSIONS: Besides the AP and lateral projections, an anteromedial oblique view of 30° certifies to be a very useful means for evaluation of the fracture reduction quality of anteromedial cortical apposition.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Fémur/diagnóstico por imagen , Fémur/cirugía , Fluoroscopía , Fijación de Fractura , Fijación Interna de Fracturas , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Humanos
20.
Ann Plast Surg ; 84(5): 580-587, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31663937

RESUMEN

BACKGROUNDS: Distally based perforator propeller flap from the lower leg region is a versatile local reconstructive technique for the foot and ankle defects. However, flap venous congestion remains a tough nut to crack. We hypothesize that raising an adipofascial flap with turnover mode of transposition can improve venous drainage and enhance flap safety. METHODS: Based on the 2 rows of septocutaneous perforators in the posterior distal third of the lower leg, distally based adipofascial flap was raised from medial sural region nourished by 1 perforator bundle from the posterior tibial artery or from the lateral sural region from the peroneal artery. The superficial dissection was performed in subdermal plane and deep in to the subfascial space. The flap was nourished by perforator-plus-adipofascial pedicle and turned over 180 degrees upside down to reach the distal wounds. One week later, a split-skin graft was used to cover the exposed fascial flap. Postoperatively, flap survival, complications, and patient functional recovery were evaluated. RESULTS: Distally based sural turnover adipofascial flaps were used in 12 cases with complicated wounds of the distal third lower leg, foot, and ankle region. All wounds were caused by trauma and experienced fracture implants fixation and 5 with osteomyelitis. The comorbidities include diabetes in 9 cases and smoking in 7. There were 8 medial ural flaps and 4 lateral sural flaps. The adipofiscial flaps measured from 6.0 cm × 5.0 cm to 17.0 cm × 6.0 cm (mean, 61.3 cm). Postoperatively, all flaps survived uneventfully without any complication such as flap ischemia and/or necrosis. Two minor donor site complications were encountered, one was postoperative hematoma, and another was hyperproliferative scar. After a mean of 14.6 months of follow-up, the adipofascial flap plus skin graft showed a durable esthetic coverage, with normal shoe wearing and walking. CONCLUSIONS: Distally based sural adipofascial turnover flap is a simple and reliable wound coverage technique. It avoids venous congestion as usually seen in distally based fasciocutaneous flaps.


Asunto(s)
Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Tobillo/cirugía , Humanos , Extremidad Inferior , Trasplante de Piel , Traumatismos de los Tejidos Blandos/cirugía , Resultado del Tratamiento
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