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1.
J Ethnopharmacol ; 331: 118274, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697410

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.


Assuntos
Medicamentos de Ervas Chinesas , Lipopolissacarídeos , Síndrome do Ovário Policístico , Transdução de Sinais , Receptor 4 Toll-Like , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/induzido quimicamente , Animais , Feminino , Receptor 4 Toll-Like/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Resistência à Insulina , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Desidroepiandrosterona/farmacologia , Cápsulas , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia
2.
Plant Cell Physiol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619117

RESUMO

Verticillium dahliae is a kind of pathogenic fungus that brings about wilt disease and great losses in cotton. The molecular mechanism of the effectors in V. dahliae regulating cotton immunity remains largely unknown. Here we identified an effector of V. dahliae, VdPHB1, whose gene expression is highly induced by infection. VdPHB1 protein is localized in the intercellular space of cotton plants. Knockout VdPHB1 gene in V. dahliae had no effect on pathogen growth, but decreased the virulence in cotton. VdPHB1 ectopically expressed Arabidopsis plants were growth-inhibited and significantly susceptible to V. dahliae. Further, VdPHB1 interacted with the type II metacaspase GhMC4. GhMC4 gene silenced cotton plants were more sensitive to V. dahliae with reduced expressions of pathogen defense-related and programmed cell death genes. The accumulation of GhMC4 protein were concurrently repressed when VdPHB1 protein expressed during infection. In summary, these results revealed a novel molecular mechanism of virulence regulation that the secreted effector VdPHB1 represses the activity of cysteine protease for helping V. dahliae infection in cotton.

3.
Int J Immunogenet ; 51(3): 130-142, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38462560

RESUMO

Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1ß/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.


Assuntos
Quimiocinas , Macrófagos , Monócitos , Osteoartrite , Humanos , Osteoartrite/imunologia , Osteoartrite/patologia , Osteoartrite/metabolismo , Quimiocinas/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Cartilagem Articular/patologia , Cartilagem Articular/imunologia , Cartilagem Articular/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Membrana Sinovial/metabolismo
4.
Lab Med ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527227

RESUMO

Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.

5.
Cancer Res ; 84(8): 1221-1236, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38330147

RESUMO

Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in nonmalignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Because fibroblasts have profound impacts on pancreatic cancer progression, we investigated whether age-related changes in pancreatic fibroblasts influence cancer growth and metastasis. Proteomics analysis revealed that aged fibroblasts secrete different factors than young fibroblasts, including increased growth/differentiation factor 15 (GDF-15). Treating young mice with GDF-15 enhanced tumor growth, whereas aged GDF-15 knockout mice showed reduced tumor growth. GDF-15 activated AKT, rendering tumors sensitive to AKT inhibition in an aged but not young microenvironment. These data provide evidence for how aging alters pancreatic fibroblasts and promotes tumor progression, providing potential therapeutic targets and avenues for studying pancreatic cancer while accounting for the effects of aging. SIGNIFICANCE: Aged pancreatic fibroblasts secrete GDF-15 and activate AKT signaling to promote pancreatic cancer growth, highlighting the critical role of aging-mediated changes in the pancreatic cancer microenvironment in driving tumor progression. See related commentary by Isaacson et al., p. 1185.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Pancreáticas , Animais , Camundongos , Fator 15 de Diferenciação de Crescimento/genética , Fator 15 de Diferenciação de Crescimento/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Neoplasias Pancreáticas/patologia , Pâncreas/patologia , Fibroblastos/patologia , Microambiente Tumoral , Linhagem Celular Tumoral , Fibroblastos Associados a Câncer/patologia
6.
PLoS One ; 19(2): e0297325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346068

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. METHODS: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. RESULTS: Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. CONCLUSION: In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Linfócitos do Interstício Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Linfócitos T CD8-Positivos , Inflamação/patologia , Prognóstico , Microambiente Tumoral
7.
bioRxiv ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38370748

RESUMO

Circulating extracellular vesicles (EVs) have gained significant attention for discovering tumor biomarkers. However, isolating EVs with well-defined homogeneous populations from complex biological samples is challenging. Different isolation methods have been found to derive different EV populations carrying different molecular contents, which confounds current investigations and hinders subsequent clinical translation. Therefore, standardizing and building a rigorous assessment of isolated EV quality associated with downstream molecular analysis is essential. To address this need, we introduce a statistical algorithm (ExoQuality Index, EQI) by integrating multiple EV characterizations (size, particle concentration, zeta potential, total protein, and RNA), enabling direct EV quality assessment and comparisons between different isolation methods. We also introduced a novel capture-release isolation approach using a pH-responsive peptide conjugated with NanoPom magnetic beads (ExCy) for simple, fast, and homogeneous EV isolation from various biological fluids. Bioinformatic analysis of next-generation sequencing (NGS) data of EV total RNAs from pancreatic cancer patient plasma samples using our novel EV isolation approach and quality index strategy illuminates how this approach improves the identification of tumor associated molecular markers. Results showed higher human mRNA coverage compared to existing isolation approaches in terms of both pancreatic cancer pathways and EV cellular component pathways using gProfiler pathway analysis. This study provides a valuable resource for researchers, establishing a workflow to prepare and analyze EV samples carefully and contributing to the advancement of reliable and rigorous EV quality assessment and clinical translation.

8.
Medicine (Baltimore) ; 103(6): e37137, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335421

RESUMO

RATIONALE: Intraosseous hemangioma is a rare benign vascular tumor of the bone that can affect any body part; however, the most common site is the vertebra, followed by calvarial bones. PATIENT CONCERNS: We present a case of intraosseous hemangioma in a 23-year-old male who presented a feeling of fullness in the throat for 3 months. The hyoid bone level had a hard mass of about 5 cm. Fine needle aspiration showed 5 mL dark bloody aspirates. Magnetic resonance image showed a 5.3 cm mixed signal intensity lesion in the hyoid body. DIAGNOSIS: Histopathologic examination showed intraosseous hemangioma with aneurysmal bone cyst (ABC)-like changes in the hyoid bone. INTERVENTIONS: The mass was completely removed without significant problems. OUTCOMES: Complete mass excision and symptomatic improvements were achieved, and no subsequent relapses were observed. LESSONS: The authors experienced a case of intraosseous hemangioma with ABC-like changes. There has been no case report of intraosseous hemangioma in the hyoid bone. This case showed a spectral pattern of the ABC-like changes developing from the underlying bone tumor as a secondary change. ABC-like changes in bone tumors can mislead the diagnosis. Careful examination of the tumor is essential for the correct diagnosis of ABC or ABC-like changes.


Assuntos
Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Hemangioma , Lesões do Pescoço , Crânio/anormalidades , Coluna Vertebral/anormalidades , Malformações Vasculares , Neoplasias Vasculares , Masculino , Humanos , Adulto Jovem , Adulto , Osso Hioide/diagnóstico por imagem , Osso Hioide/cirurgia , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Crânio/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Coluna Vertebral/patologia
9.
Childs Nerv Syst ; 40(2): 549-553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37552306

RESUMO

Angiolipomas are slow-growing benign mesenchymal-derived tumors consisting of mature adipocytes and thin-walled blood vessels. While the majority of angiolipomas are found in subcutaneous tissues, rarely there are case reports of intracranial lesions. We present a case of cisternal angiolipoma in a 10-year-old female. She presented with vague symptoms like dizziness without neurological deficits and radiological evaluation confirmed a left-sided infratentorial cisternal partially enhancing mass. She underwent craniotomy and had complete resection of the mass, which was histologically composed of mature adipocytes and blood vessels, consistent with angiolipoma. A review of the literature found only 18 cases of intracranial angiolipoma ever reported with our case representing the first case of infratentorial cisternal region.


Assuntos
Angiolipoma , Feminino , Humanos , Criança , Angiolipoma/diagnóstico por imagem , Angiolipoma/cirurgia , Radiografia , Tela Subcutânea/patologia , Tela Subcutânea/cirurgia , Craniotomia
10.
J Vasc Surg Venous Lymphat Disord ; 12(1): 101669, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37625507

RESUMO

OBJECTIVE: The objective of this study was to compare the outcomes of pharmacomechanical thrombolysis and thrombectomy (PCDT) plus catheter-directed thrombolysis (CDT) vs CDT alone for the treatment of acute iliofemoral deep vein thrombosis (DVT) and summarize the clinical experience, safety outcomes, and short- and long-term efficacy. METHODS: We performed a 4-year retrospective, case-control study. A total of 95 consecutive patients with acute symptomatic iliofemoral deep vein thrombosis (DVT) with a symptom duration of ≤7 days involving the iliac and/or common femoral veins underwent endovascular interventions. The patients were divided into two groups according to their clinical indications: PCDT plus CDT vs CDT alone. Statistical analyses were used to compare the clinical characteristics and outcomes between the two groups. Additionally, the patients were followed up for 3 to 36 months after treatment, and the proportions of post-thrombotic syndrome (PTS) and moderate to severe PTS were analyzed using the Kaplan-Meier survival method. RESULTS: A total of 95 consecutive patients were analyzed in this retrospective study, of whom, 51 underwent CDT alone and 44 underwent PCDT plus CDT. Between the two groups, in terms of immediate-term efficacy and safety, significant differences were found in the catheter retention time (60.64 ± 12.04 hours vs 19.42 ± 4.04 hours; P < .001), dosages of urokinase required (5.82 ± 0.81 million units vs 1.80 ± 0.64 million units; P < .001), the detumescence rate at 24 hours postoperatively (48.46% ± 8.62% vs 76.79% ± 7.98%; P = .026), the descent velocity of D-dimer per day (2266.28 ± 1358.26 µg/L/D vs 3842.34 ± 2048.02 µg/L/D; P = .018), total hospitalization stay (6.2 ± 1.40 days vs 3.8 ± 0.70 days; P = .024), number of postoperative angiograms (2.4 ± 0.80 vs 1.2 ± 0.30; P = .042), and grade III venous patency (>95% lysis: 54.5% vs 68.6%; P = .047). Furthermore, during the follow-up period, significant differences were found in the incidence of PTS (Villalta scale ≥5 or a venous ulcer: 47.0% vs 27.7%; P = .037), and the incidence proportion of moderate to severe PTS at 12 months (15.7% vs 4.5%; P = .024) and 24 months (35.3% vs 11.4%; P = .016). CONCLUSIONS: Compared with CDT alone, in the iliofemoral DVT subgroup with a symptom duration of ≤7 days, PCDT plus CDT could significantly relieve early leg symptoms, shorten the hospitalization stay, reduce bleeding complications, promote long-term venous patency, and decrease the occurrence of PTS and the incidence proportion of moderate to severe PTS. Thus, the short- and long-term outcomes both support the superiority of PCDT plus CDT vs CDT in this subgroup.


Assuntos
Síndrome Pós-Trombótica , Trombose Venosa , Humanos , Estudos Retrospectivos , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Fibrinolíticos , Estudos de Casos e Controles , Resultado do Tratamento , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/cirurgia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Trombose Venosa/complicações , Síndrome Pós-Trombótica/diagnóstico por imagem , Síndrome Pós-Trombótica/etiologia , Síndrome Pós-Trombótica/terapia , Catéteres/efeitos adversos , Doença Aguda
11.
Int Wound J ; 21(3): e14444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37953697

RESUMO

This meta-analysis aimed to evaluate the efficacy of Traditional Chinese Medicine (TCM) in enhancing surgical site wound healing following colorectal surgery. We systematically reviewed and analysed randomized controlled trials (RCTs) that investigated the outcomes of TCM interventions in postoperative wound management, adhering to the PRISMA guidelines. The primary outcome was the assessment of wound healing through the REEDA (redness, oedema, ecchymosis, discharge and approximation) scale at two different time points: the 10th day and 1-month post-surgery. Seven RCTs involving 1884 patients were included. The meta-analysis revealed a statistically significant improvement in wound healing in the TCM-treated groups compared to the control groups at both time intervals. On the 10th day post-surgery, the TCM groups exhibited a significant reduction in REEDA scale scores (I2 = 98%; random: SMD: -2.25, 95% CI: -3.52 to -0.98, p < 0.01). A similar trend was observed 1-month post-surgery, with the TCM groups showing a substantial decrease in REEDA scale scores (I2 = 98%; random: SMD: -3.39, 95% CI: -4.77 to -2.01, p < 0.01). Despite the promising results, the majority of the included studies were of suboptimal quality, indicating a need for further high-quality RCTs to substantiate the findings. The results suggest that TCM interventions can potentially enhance wound healing post-colorectal surgery, paving the way for further research in this area to validate the efficacy of TCM in postoperative management.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Medicina Tradicional Chinesa/métodos , Cicatrização
12.
World Neurosurg ; 182: e854-e865, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104931

RESUMO

BACKGROUND: We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS: We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. RESULTS: Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. CONCLUSIONS: Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.


Assuntos
Cistos , Malformações Arteriovenosas Intracranianas , Radiocirurgia , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/radioterapia , Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Cistos/diagnóstico por imagem , Cistos/etiologia , Cistos/patologia , Encéfalo/patologia , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Seguimentos
13.
J Cachexia Sarcopenia Muscle ; 15(1): 149-158, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38123146

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS: Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS: Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS: Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias de Cabeça e Pescoço , Neoplasias Pancreáticas , Humanos , Caquexia/genética , Caquexia/complicações , Estudos Retrospectivos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/complicações
14.
BMC Complement Med Ther ; 23(1): 458, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102584

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated. METHODS: Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein-protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR. RESULTS: The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug-disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways. DISCUSSION: This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.


Assuntos
Cistos Ovarianos , Neoplasias Ovarianas , Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Camundongos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Farmacologia em Rede , PPAR gama , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Biologia Computacional
15.
J Neurosurg Case Lessons ; 6(14)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37782958

RESUMO

BACKGROUND: A pseudoaneurysm of the superficial temporal artery is an uncommon clinical entity that has largely been linked with direct traumatic causes. Neurofibromatosis type 1 (NF1)-related vasculopathy is a rare cause of idiopathic arterial bleeding in the craniofacial region. OBSERVATIONS: A 46-year-old male with clinical features of NF1 presented to the hospital with an enlarging and tender right temporal mass without a history of trauma. Computed tomography angiography suggested the development of a pseudoaneurysm, and surgery was performed to resect the mass. Histopathological examinations showed focal interruption of the epithelium layer and elastic lamina, well-demarcated thickening of the smooth muscle layers of the arterial wall, supporting the diagnosis of pseudoaneurysm. LESSONS: NF1-associated vasculopathy is likely the predisposing factor for the development of a superficial temporal artery pseudoaneurysm.

16.
Eur J Pharmacol ; 959: 176073, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37742813

RESUMO

Hederagenin is a pentacyclic triterpenoid that is widely distributed as the main pharmaceutical ingredient in various medicinal plants. Similarly as other pentacyclic triterpenoids, hederagenin has various pharmacological effects such as anti-tumor, anti-inflammatory, anti-depressant, and anti-viral activities. In particular, the anti-tumor activity of hederagenin indicates its potential for development into highly effective chemotherapeutic agents. Studies revealed that hederagenin effectively suppresses the growth of various tumor cell lines in vitro and interacts with several molecular targets that play essential roles in various cellular signaling pathways. The compound suppresses transformation, inhibits proliferation, and induces apoptosis in tumor cells. In this review, we highlight research progress on the source, pharmacokinetics, pharmacological activity, and mechanism of action of hederagenin and the anti-tumor activity of its analogs by integrating and analyzing relevant domestic and international studies and providing a basis for their further development and application.


Assuntos
Ácido Oleanólico , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Linhagem Celular Tumoral , Triterpenos Pentacíclicos , Anti-Inflamatórios
17.
Arch Craniofac Surg ; 24(4): 189-192, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37654240

RESUMO

An intraosseous hemangioma of the frontal bone is typically removed via a coronal incision. This procedure, while effective, can be lengthy and may result in complications such as a prominent scar and hair loss. An alternative approach involves a direct incision in the forehead, which leaves a less noticeable scar and allows a quicker recovery. However, in this specific case, the patient declined both coronal surgery and surgery through a direct forehead incision due to cosmetic concerns. Therefore, we proposed an anterior hairline incision. A 35-year-old woman presented with a firm, non-mobile, palpable mass on her right forehead. Preoperative non-contrast computed tomography revealed a heterogeneous osteolytic lesion. We performed an excisional biopsy through the anterior hairline. Postoperative non-contrast computed tomography was conducted 2 and 6 months after surgery. The wound was clean and free of complications, and there was no local recurrence. Partial resection can reduce scarring for patients who are concerned about cosmetic outcomes. However, the potential for recurrence remains a significant concern. We present this case of an anterior hairline incision for a hemangioma located in the forehead, evaluated using serial computed tomography for both preoperative and postoperative imaging.

18.
Nutrients ; 15(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37630786

RESUMO

The acidic tumor environment has emerged as a crucial factor influencing the metastatic potential of cancer. We investigated the effect of an acidic environment on the acquisition of metastatic properties in MCF7 breast cancer cells and explored the inhibitory effects of gallic acid. Prolonged exposure to acidic culture conditions (over 12 weeks at pH 6.4) induced the acquisition of migratory and invasive properties in MCF7 cells, accompanied by increased expression of Matrix Metalloproteinase 2 and 9 (MMP2 and MMP9, respectively), together with alterations in E-cadherin, vimentin, and epithelial-to-mesenchymal transition markers. Gallic acid effectively inhibited the survival of acidity-adapted MCF7 (MCF7-6.4/12w) cells at high concentrations (>30 µM) and reduced metastatic characteristics induced by acidic conditions at low concentration ranges (5-20 µM). Moreover, gallic acid suppressed the PI3K/Akt pathway and the nuclear accumulation of ß-catenin, which were elevated in MCF7-6.4/12w cells. These findings highlight the potential of gallic acid as a promising therapeutic agent for metastatic traits in breast cancer cells under acidic conditions.


Assuntos
Metaloproteinase 2 da Matriz , Neoplasias , Humanos , Ácido Gálico/farmacologia , Células MCF-7 , Fosfatidilinositol 3-Quinases , Azia
20.
J Med Food ; 26(8): 595-604, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37594560

RESUMO

Acorn (Quercus acutissima CARR.) has been used in traditional food and medicinal ethnopharmacology in Asia, and it has shown multifarious functions such as antidementia, antiobesity, and antiasthma functions. However, there is limited scientific evidence about the efficacy of acorn for ameliorating skin problems. Treatment with ethanol-extracted acorns (EeA's) ablated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-8 stimulated by tumor necrosis factor (TNF)-α in human adult low calcium high temperature (HaCaT) cells under sublethal dosages. In addition, treatment with EeA dose dependently inhibited the ex vivo hyper keratin formation induced by TNF-α in HaCaT cells in conjunction with the blockade of cytokeratin-1 (CK-1) and cytokeratin-5 (CK-5) expression. Moreover, EeA treatment stimulated the expression of hyaluronic acid (HA) expression in human fibroblasts in a dose-dependent manner. Linoleamide was identified as the functional component of EeA using preparative high-performance liquid chromatography and ultra high performance liquid chromatography-mass spectrometry-mass spectrometry analysis, and the anti-inflammatory features and enhanced HA expression were verified. Collectively, these results suggest the efficacy of EeA supplementation in improving skin problems via anti-inflammation and upregulating HA production.


Assuntos
Ácido Hialurônico , Quercus , Adulto , Humanos , Queratinócitos , Células HaCaT , Etanol
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