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2.
Int J Mol Sci ; 25(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38673726

RESUMO

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.


Assuntos
Neoplasias Ósseas , Raios Infravermelhos , Terapia Fototérmica , Humanos , Neoplasias Ósseas/terapia , Terapia Fototérmica/métodos , Raios Infravermelhos/uso terapêutico , Animais , Fármacos Fotossensibilizantes/uso terapêutico , Osteossarcoma/terapia , Osteossarcoma/patologia , Terapia Combinada/métodos , Imunoterapia/métodos , Fotoquimioterapia/métodos , Regeneração Óssea
3.
Cell Rep ; 43(3): 113963, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38492218

RESUMO

T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.


Assuntos
Tecido Adiposo , Linfócitos T , Camundongos , Animais , Linfócitos T/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Inflamação/patologia , Células-Tronco/metabolismo
4.
Cancer Res ; 84(11): 1889-1897, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38536116

RESUMO

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy. SIGNIFICANCE: Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.


Assuntos
Aspirina , Inibidores de Hidroximetilglutaril-CoA Redutases , Inflamação , Neoplasias , Humanos , Aspirina/uso terapêutico , Neoplasias/prevenção & controle , Neoplasias/epidemiologia , Feminino , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Adulto , Fatores de Risco , Reino Unido/epidemiologia
5.
Front Oncol ; 14: 1331815, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549939

RESUMO

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

6.
Mitochondrion ; 75: 101846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237649

RESUMO

Due to the pivotal role of mitochondria in the generation of adenosine triphosphate (ATP) and the regulation of cellular homeostasis, mitochondrial dysfunction may exert a profound impact on various physiological systems, potentially precipitating a spectrum of distinct diseases. Consequently, research pertaining to mitochondrial therapeutics has assumed increasing significance, warranting heightened scrutiny. In recent years, the field of mitochondrial therapy has witnessed noteworthy advancements, with active exploration into diverse pharmacological agents aimed at ameliorating mitochondrial function. Elamipretide (SS-31), a novel synthetic mitochondrial-targeted antioxidant, has emerged as a promising candidate with extensive therapeutic potential. Its notable attributes encompass the mitigation of oxidative stress, the suppression of inflammatory processes, the maintenance of mitochondrial dynamics, and the prevention of cellular apoptosis. As such, SS-31 may emerge as a viable choice for the treatment of mitochondrial dysfunction-related ailments in the foreseeable future. This article extensively expounds upon the superiority of SS-31 over natural antioxidants and traditional mitochondrial-targeted antioxidants, delves into its mechanisms of modulating mitochondrial function, and comprehensively summarizes its applications in alleviating mitochondrial dysfunction-associated disorders. Furthermore, we offer a comprehensive outlook on the expansive prospects of SS-31's future development and application.


Assuntos
Antioxidantes , Doenças Mitocondriais , Humanos , Antioxidantes/metabolismo , Mitocôndrias/metabolismo , Peptídeos/farmacologia , Estresse Oxidativo , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo
7.
J Dermatol ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38292003

RESUMO

Porokeratotic adnexal ostial nevus (PAON) is a rare adnexal hamartoma characterized by keratotic papules following Blaschko's lines, typically located on the unilateral distal extremities. Cutaneous somatic GJB2 mutations have been linked to the pathogenesis of PAON. However, the genetic mechanism underlying bilateral or extended forms, which are less documented, remains unknown. In this study, we presented two cases of PAON with widespread cutaneous lesions and scalp involvement, and demonstrated the presence of GJB2 mosaic mutations in both patients. We further investigated the mosaic frequency in different tissues to gain insights into the mutation events contributing to the phenotype of widespread PAON. Our findings suggest that early postzygotic mutation causing mosaic GJB2 mutations may contribute to the widespread phenotype of PAON, thereby enriching the disease spectrum and mutation profile of PAON.

8.
Bioorg Chem ; 143: 106981, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37995645

RESUMO

The combination of chemodynamic therapy and photothermal therapy has a promising application owing to its impressive anti-cancer effects. However, the degradability of the material and the lack of targeting severely limit its further clinical application. Herein, DNAs containing nucleolin aptamer (AS1411) and different bases sequences were used to functionalize PB NPs for the targeted treatment. Compared to prussian blue, DNA-functionalized prussian blue does not reduce the photothermal properties of prussian blue. Moreover, DNA confers DNA-functionalized prussian blue targeting and higher enzymatic activity, thereby achieving a more effective combination of chemodynamic and photothermal treatment. The therapeutic efficacy of this nanoplatform was evaluated in vivo and in vitro experiments, exhibiting that DNA-functionalized prussian blue nanozyme can maximize the precise control of the therapeutic effect, reduce the toxic and side effects caused by non-specific accumulation on other normal cells, and effectively achieve targeted killing of cancer cells. This work demonstrates that DNA-functionalized prussian blue can improve the efficiency of combined tumor treatment and enhance the application value of prussian blue in tumor treatment, which is expected to provide theoretical support for clinical application.


Assuntos
Ferrocianetos , Nanopartículas , Neoplasias , Humanos , Terapia Combinada , Neoplasias/terapia , DNA
9.
Chemistry ; 30(11): e202302878, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38103037

RESUMO

High-contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue-based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical "OFF-to-ON" absorption transition for high-contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue-based probe for cysteine (MB-Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π-conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130-fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high-contrast manner. Therefore, this work established an up-to-date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo.


Assuntos
Neoplasias , Técnicas Fotoacústicas , Azul de Metileno , Cisteína , Técnicas Fotoacústicas/métodos , Diagnóstico por Imagem , Imagem Óptica
10.
Zhen Ci Yan Jiu ; 48(12): 1266-1273, 2023 Dec 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38146250

RESUMO

OBJECTIVES: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity. METHODS: PCOS patients with abdominal obesity were randomly divided into low-frequency group (n=29) and dilatational wave group (n=29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. RESULTS: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency (P<0.01, P<0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score (P<0.01, P<0.05);the dilatational wave group showed decreased serum AMH contents (P<0.05) and increased serum SHBG contents (P<0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased (P<0.01, P<0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction (P<0.05) in WC after treatment. CONCLUSIONS: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.


Assuntos
Acne Vulgar , Eletroacupuntura , Síndrome do Ovário Policístico , Feminino , Humanos , Obesidade Abdominal/terapia , Qualidade de Vida , Síndrome do Ovário Policístico/terapia , Dismenorreia , Pontos de Acupuntura , Obesidade/terapia
11.
Front Cell Dev Biol ; 11: 1277686, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941898

RESUMO

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions. Emerging studies reported that TLR signaling plays an important role in bone remodeling by directly impacting MSC osteogenic differentiation or osteoimmunology. However, how to regulate TLR signaling is critical and remains to be elucidated to promote the osteogenic differentiation of MSCs and new bone formation for bone tissue repair. This review outlines distinct TLR variants on MSCs from various tissues, detailing the impact of TLR pathway activation or inhibition on MSC osteogenic differentiation. It also elucidates TLR pathways' interplay with osteoclasts, immune cells, and extracellular vesicles (EVs) derived from MSCs. Furthermore, we explore biomaterial-based activation to guide MSCs' osteogenic differentiation. Therefore, understanding TLRs' role in this context has significant implications for advancing bone regeneration and repair strategies.

12.
Nanoscale ; 15(41): 16727-16733, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37811862

RESUMO

Nanoprobes based on lanthanide-doped upconversion nanoparticles (UCNPs) exhibit promising potential in bioimaging and biosensing due to their unique optical properties. However, conventional UCNP nanoprobes based on the dye quenching effect are still limited in biosensing due to their low upconversion efficiency. The advent of dye-sensitized upconversion has resulted in nanoprobes with significantly enhanced efficiency; however, these still suffer from a high initial emissive background. In view of this, herein, we have constructed a dye-quenched/sensitized switching upconversion nanoprobe for high-contrast imaging of the pH-related tumor microenvironment. Under normal conditions, the luminescence of the nanoprobe at 540 nm (UCL540) was significantly quenched by the employed dye. Upon being triggered by an acid, the dye would switch to its fluorescent form to sensitize the luminescence of UCNPs, affording a significant enhancement of UCL540. The switching from dye-quenched UCL to dye-sensitized UCL jointly enables the detection of a high signal-to-background ratio (high up to 50), allowing for high-contrast mapping of the tumor specific acidic microenvironment in vivo. We believe that this nanoplatform holds considerable promise for acid-related sensing.


Assuntos
Nanopartículas , Microambiente Tumoral , Luminescência , Diagnóstico por Imagem , Concentração de Íons de Hidrogênio
13.
Transpl Immunol ; 81: 101935, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37739235

RESUMO

Ovaries are important reproductive and endocrine organs in women. Ovarian tissue cryopreservation and transplantation technology can not only solve the fertility problems of patients, but also may improve female endocrine problems. This is particularly important for patients in urgent need of radiotherapy and chemotherapy, and for women with prepubertal malignant tumors. However, follicle loss after freeze-thawing is a key challenge for effective ovarian tissue transplantation and leads to poor transplant outcomes. Therefore, it is crucial to elucidate the mechanisms underlying follicle loss after transplantation. This paper reviews current research on the mechanisms of follicle loss after frozen-thawed ovarian tissue transplantation, including the activation, apoptosis, and pyroptosis mechanisms of primordialfollicles. Further, it highlights the requirement of more experimental studies for improving ovarian tissue transplantation methods.


Assuntos
Folículo Ovariano , Ovário , Feminino , Humanos , Ovário/fisiologia , Folículo Ovariano/fisiologia , Criopreservação , Apoptose
15.
Acta Biomater ; 170: 427-441, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37634831

RESUMO

Accumulating studies demonstrated that hydroxyapatite nanoparticles (HANPs) showed a selective anti-tumor effect, making them a good candidate for osteosarcoma (OS) treatment. However, the capacity of HANPs with different aspect ratios to regulate tumor immune microenvironment (TIM) was scarcely reported before. To explore it, the three HANPs with aspect ratios from 1.86 to 6.25 were prepared by wet chemical method. After a 24 or 72 h-exposure of OS UMR106 cells or macrophages to the nanoparticles, the tumor cells exhibited immunogenic cell death (ICD) indicated by the increased production of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), and macrophages were activated with the release of pro-inflammatory cytokines. Next, the beneficial crosstalk between tumor cells and macrophages generated in the presence of HANPs for improved anti-tumor immunity activation. In the OS-bearing cognate rat model, HANPs inhibited OS growth, which was positively correlated with CRT and HMGB1 expression, and macrophage polarization in the tumor tissues. Additionally, HANPs promoted CD8+ T cell infiltration into the tumor and systemic dendritic cell maturation. Particularly, HANPs bearing the highest aspect ratio exhibited the strongest immunomodulatory and anti-tumor function. This study suggested the potential of HANPs to be a safe and effective drug-free nanomaterial to control the TIM for OS therapy. STATEMENT OF SIGNIFICANCE: Emerging studies demonstrated that hydroxyapatite nanoparticles (HANPs) inhibited tumor cell proliferation and tumor growth. However, the underlying anti-tumor mechanism still remains unclear, and the capacity of HANPs without any other additive to regulate tumor immune microenvironment (TIM) was scarcely reported before. Herein, we demonstrated that HANPs, in an aspect ratio-dependent manner, showed the potential to delay the growth of osteosarcoma (OS) and to regulate TIM by promoting the invasion of CD8+ T cells and F4/80+ macrophages, and inducing immunogenic cell death (ICD) in tumors. This work revealed the new molecular mechanism for HANPs against OS, and suggested HANPs might be a novel ICD inducer for OS treatment.


Assuntos
Neoplasias Ósseas , Proteína HMGB1 , Nanopartículas , Osteossarcoma , Ratos , Animais , Durapatita/farmacologia , Durapatita/química , Linfócitos T CD8-Positivos , Osteossarcoma/tratamento farmacológico , Nanopartículas/química , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
17.
Acta Biomater ; 164: 626-640, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37086827

RESUMO

Macrophages represent the most prevalent immune cells in the tumor micro-environment, making them an appealing target for tumor immunotherapy. One of our previous studies showed that hydroxyapatite nanoparticles (HANPs) enhanced Toll-like receptor 4 (TLR4) signal transduction in macrophages. This study was proposed to investigate how HANPs manipulated the phenotype and function of macrophage against 4T1 breast tumors in the presence or absence of MPLA, a low toxic Toll-like receptor 4 (TLR4) agonist. The results demonstrated that the addition of HANPs to MPLA significantly promoted cytokine secretion and macrophage polarization toward a tumoricidal M1 phenotype. Further, the resulting supernatant from HANPs/MPLA co-stimulated macrophages enhanced 4T1 tumor cells apoptosis compared to that from macrophages treated with a single component or PBS control. In particular, we found HANPs elicited immunogenic cell death (ICD) indicated by the increased expression of "danger signals", including HMGB1, CRT and ATP in 4T1 cells. Subsequently, the ICD derivatives-containing supernatant from HANPs-treated 4T1 cells activated macrophage and shifted the phenotype of the cells toward M1 type. Moreover, in a tumor-bearing mice model, HANPs and MPLA synergistically delayed tumor growth compared to PBS control, which was positively associated with the promoted macrophage polarization and ICD induction. Therefore, our findings demonstrated a potential platform to modulate the function of macrophages, and shed a new insight into the mechanism involving the immunomodulatory effect of HANPs for tumor therapy. STATEMENT OF SIGNIFICANCE: Polarizing macrophage toward tumoricidal phenotype by harnessing Toll-like receptor (TLR) agonists has been proven effective for tumor immunotherapy. However, the immunomodulatory potency of TLR agonists is limited due to immune suppression or tolerance associated with TLR activation in immune cells. Herein, we introduced hydroxyapatite nanoparticles (HANPs) to MPLA, a TLR4 agonist. The results demonstrated that the addition of HANPs to MPLA promoted macrophage shift toward tumoricidal M1 phenotype, supported a "hot" tumor transformation, and delayed 4T1 tumor growth. Moreover, we found that HANPs elicited immunogenic cell death that produced "danger" signals from cancer cells thereby further facilitated macrophage polarization. This work is significant to direct the rational design of HANPs coupled with or without TLR agonists for tumor immunotherapy.


Assuntos
Nanopartículas , Receptor 4 Toll-Like , Animais , Camundongos , Receptor 4 Toll-Like/metabolismo , Durapatita/farmacologia , Durapatita/metabolismo , Macrófagos/metabolismo , Adjuvantes Imunológicos/farmacologia , Ativação de Macrófagos
18.
Sci China Life Sci ; 66(8): 1831-1840, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37121939

RESUMO

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.


Assuntos
Desnutrição , Neoplasias , Humanos , Masculino , Avaliação Nutricional , Estado Nutricional , Desnutrição/diagnóstico , Programas de Rastreamento/métodos , Neoplasias/diagnóstico
19.
Biomed Res Int ; 2023: 5124034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660452

RESUMO

Background: Galactose-deficient IgA1 (Gd-IgA1) is a critical initiating factor in the pathogenesis of IgA nephropathy (IgAN), which plays an important role in the diagnosis and evaluation of this disease. Moreover, the whole pathogenesis process has an intimate association with the immune response of T and B lymphocytes and their inflammatory factors. There is no specific therapy for IgAN at present. Yiqi Yangyin Formula can significantly reduce urinary protein and hematuria in patients with IgAN. Yiqi Yangying Heluo Formula (YYHF) is optimized on the basis of the above prescription, but its specific mechanism remains to be further studied. Methods: The effect of YYHF on urinary protein and urinary red blood cell count in patients with IgAN was observed by a self-controlled clinical study before and after treatment. On this basis, flow cytometry was used to detect the proportion of T lymphocyte subsets in peripheral blood of patients with IgAN before and after treatment and healthy controls. Meanwhile, the levels of Gd-IgA1, B cell activation factor (BAFF), and their cytokines (IL-4, IL-6, and IL-17) in peripheral blood were detected by enzyme-linked immunosorbent assay. The changes in mechanism-related indicators of the two groups were observed and subject to correlation analysis. Results: (1) Compared with the levels before treatment, 24-hour urinary protein content decreased by 47.7% and urinary red blood cell number decreased by 67% in patients with IgAN intervened by YYHF after 48 weeks of follow-up. (2) Compared with the healthy control group, patients with IgAN showed a significantly increased proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg, obviously reduced proportion of Th2 cells and Treg cells, and evidently elevated levels of Gd-IgA1, BAFF, and their cytokines (IL-4, IL-6, and IL-17) in the peripheral blood. (3) Following 48 weeks of follow-up after intervention treatment with YYHF, the levels of Gd-IgA1, BAFF, IL-6, and IL-17 were significantly lower, but the level of IL-4 was higher in peripheral blood of patients with IgAN than those before treatment and after 24 weeks of treatment; simultaneously, the proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg decreased while that of Th2 cells and Treg cells increased after 48 weeks of follow-up compared with that before treatment in peripheral blood of patients with IgAN. (4) The results of correlation analysis revealed that the level of Gd-IgA1 in peripheral blood of patients with IgAN was positively correlated with the level of BAFF, as well as the proportion of Th1 cells, Th17 cells, Th1/Th2, IL-6, and IL-17 levels, and negatively correlated with the proportion of Treg cells. In addition, the level of Gd-IgA1 in peripheral blood was positively correlated with proteinuria, yet without correlation with hematuria. Conclusion: YYHF can reduce the quantitative level of 24 h urinary protein and urinary red blood cell count in patients with IgAN. Patients with IgAN have obvious T cell immune imbalance. YYHF can significantly reduce the level of Gd-IgA1 in patients with IgAN, and its mechanism may be explained by the reduced level of BAFF in peripheral blood and improved immune balance of T cells.


Assuntos
Medicamentos de Ervas Chinesas , Glomerulonefrite por IGA , Humanos , Citocinas , Galactose , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/diagnóstico , Hematúria , Imunoglobulina A , Interleucina-17 , Interleucina-4 , Interleucina-6 , Medicamentos de Ervas Chinesas/uso terapêutico
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