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1.
Zhongguo Fei Ai Za Zhi ; 27(7): 541-549, 2024 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-39147709

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide, with metastasis being the primary cause of mortality in lung cancer patients, and its prevention and control efficacy remain limited. In recent years, immunotherapy has emerged as a promising direction for overcoming the bottleneck of metastasis. Macrophages, as essential components of innate immunity, participate in the entire process of tumor initiation and progression. Tumor-associated macrophages (TAMs) represent the most abundant immune population in the tumor microenvironment (TME), displaying both anti-tumor M1-like and pro-tumor M2-like phenotypes. The latter promotes tumor invasion and metastasis, angiogenesis, lymphangiogenesis, immune suppression, and reactivation of dormant disseminated tumor cells (DTCs), thereby facilitating tumor metastasis. In recent years, traditional Chinese medicine (TCM) has shown significant efficacy in inhibiting tumor metastasis and has been extensively validated. It exerts anti-tumor effects by reducing the recruitment of TAMs, inhibiting M2-like polarization, and modulating cytokines and proteins in the TME. This paper reviews the relationship between TAMs and lung cancer metastasis, elucidates the targets and mechanisms of TCM in regulating TAMs to prevent and treat lung cancer metastasis, aiming to provide insights into lung cancer prevention and treatment.
.


Assuntos
Neoplasias Pulmonares , Medicina Tradicional Chinesa , Metástase Neoplásica , Macrófagos Associados a Tumor , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Metástase Neoplásica/prevenção & controle , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Animais , Microambiente Tumoral/efeitos dos fármacos
2.
Diabetol Metab Syndr ; 16(1): 201, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160567

RESUMO

BACKGROUND: The triglyceride-glucose (TyG) index is a new and good biomarker of insulin resistance (IR). The prognostic utility of the TyG index for patients with type 2 diabetes mellitus (T2DM) remains uncertain. Our study seeks to elucidate the connection between the TyG index and adverse renal outcomes within a T2DM population, while also examining if these relationships are influenced by subgroup variations. METHODS: We analyzed data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, involving 10,196 T2DM participants, to assess the link between triglyceride-glucose levels and adverse renal outcomes. This evaluation included Restricted Cubic Spline (RCS) analysis, Kaplan-Meier survival analysis, and Multivariate Cox proportional regression. Additionally, we examined the interaction between subgroups concerning adverse renal outcomes. RESULTS: During a 7-year follow-up, 5824 patients (57.1%) experienced worsening renal function, 2309 patients (23.2%) developed albuminuria, and 280 patients (2.7%) advanced to renal failure. After adjusting for a range of confounding variables, triglyceride-glucose levels were significantly linked to both worsening renal function (p < 0.001) and the onset of albuminuria (p = 0.020). Nonetheless, no significant association was observed between triglyceride-glucose levels and renal failure (p = 0.247). Furthermore, there was no significant subgroups interaction to the associations between TyG levels and adverse renal outcomes. CONCLUSION: Our study underscores the significant relationship between the triglyceride-glucose index and the risk of adverse renal outcomes in patients with T2DM. The TyG index, as a readily calculable measure, offers clinicians a valuable tool for anticipating the risk of adverse renal outcomes in this patient population.

3.
Mol Ther Nucleic Acids ; 35(3): 102283, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39165562

RESUMO

The implementation of targeted molecular therapies and immunotherapy in melanoma vastly improved the therapeutic outcome in patients with limited efficacy of surgical intervention. Nevertheless, a large fraction of patients with melanoma still remain refractory or acquire resistance to these new forms of treatment, illustrating a need for improvement. Here, we report that the clinically relevant combination of mitogen-activated protein (MAP) kinase pathway inhibitors dabrafenib and trametinib synergize with RIG-I agonist-induced immunotherapy to kill BRAF-mutated human and mouse melanoma cells. Kinase inhibition did not compromise the agonist-induced innate immune response of the RIG-I pathway in host immune cells. In a melanoma transplantation mouse model, the triple therapy outperformed individual therapies. Our study suggests that agonist-induced activation of RIG-I with its synthetic ligand 3pRNA could vastly improve tumor control in a substantial fraction of patients with melanoma receiving MAP kinase inhibitors.

4.
World J Gastrointest Oncol ; 16(8): 3716-3722, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39171176

RESUMO

BACKGROUND: Aggressive fibromatosis (AF), also known as desmoid tumor or desmoid-type fibromatosis, is a rare soft tissue neoplasm that can occur in almost any part of the body. Although it is a benign disease, AF is aggressive and infiltrative and has a high recurrence rate after surgery. Common sites for intra-abdominal AF are the small bowel mesentery, retroperitoneum, and pelvis. AF in the colon is extremely rare. CASE SUMMARY: Here, we report the first case of sigmoid colon AF, which was accidentally discovered in a 27-year-old woman during laparoscopic myomectomy. Computed tomography confirmed a slightly enhanced mass in the sigmoid colon. Subsequent colonoscopy did not reveal a mass in the colonic lumen, but a suspected external compress was found in the sigmoid colon. Surgical disease involving a gastrointestinal stromal tumor was suspected. The patient underwent laparoscopic exploration, and sigmoidectomy with a negative margin was performed to excise the mass. Postoperative immunohistochemistry revealed that the mass was an AF. The patient recovered well and was recurrence-free at the 30-month follow-up without adjuvant therapy. CONCLUSION: AF should be considered in the differential diagnosis of subepithelial colon masses. Radical resection alone can achieve good outcomes.

5.
Heliyon ; 10(13): e33888, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39027487

RESUMO

Background: Single Tumor-associated autoantibodies (TAAbs) and tumor-associated antigens (TAAs) have been found to have lower diagnostic efficacy in lung cancer. Our objective is to develop and validate a lung cancer prediction model that utilizes TAAbs and TAAs and to enhance the accuracy of lung cancer detection. Methods: 1830 subjects were randomly divided into training and validation sets at a 7:3 ratio for this study. Lasso regression analysis was used to remove collinear variables, whereas univariate logistic regression analysis was employed to identify potential independent risk factors for lung cancer. A diagnostic model was constructed using multivariate logistic analysis. The results were presented as a nomogram and assessed for various performance measures, including area under the curve, calibration curve, and decision curve analysis. Results: The diagnostic model was developed using gender, age, GAGE7, MAGE-A1, CA125, and CEA as variables. The training set had an AUC of 0.787, while the validation set had an AUC of 0.750. The calibration curves of the training and validation sets showed a strong agreement between anticipated and observed values. The nomogram performed better than any individual variable in both the training and validation sets in terms of net benefits for lung cancer detection, according to DCA analysis. Conclusions: This study proposes a diagnostic model for lung cancer that uses TAAbs and TAAs and incorporates individual characteristics. This model can be easily applied to personalized diagnosis.

6.
Phys Rev Lett ; 132(25): 253803, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996228

RESUMO

The spin angular momentum (SAM) of an elliptically or circularly polarized light beam can be transferred to matter to drive a spinning motion. It is counterintuitive to find that a light beam without SAM can also cause the spinning of microparticles. Here, we demonstrate controllable spinning of birefringent microparticles via a tightly focused radially polarized vortex beam that has no SAM prior to focusing. To this end, the orbital Hall effect is proposed to control the radial separation of two spin components in the focused field, and tunable transfer of local SAM to microparticles is achieved by manipulating the twisted wavefront of the source light. Our work broadens the perspectives for controllable exertion of optical torques via the spin-orbit interactions.

7.
Int Endod J ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046812

RESUMO

AIM: Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold-free microtissue-based dental pulp regeneration. Surface collagen cross-linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross-linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)-derived 3D cell spheroids. METHODOLOGY: Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross-linking. Microtissue viability was examined by live/dead staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA-preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA-preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F-actin expressions. PA-preconditioned macrotissues were subjected to histological analysis, including haematoxylin-eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP-1) expressions. RESULTS: PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse-section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP-1 expressions in macrotissues. Additionally, PA preconditioning induced higher F-actin and DSPP expression in microtissues, while inhibition of F-actin activity by cytochalasin B attenuated PA-induced dimensional change and DSPP upregulation. CONCLUSION: PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC-derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold-free tissue engineering applications in regenerative dentistry.

8.
J Hazard Mater ; 476: 135015, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38943886

RESUMO

The rapid proliferation of the halophilic pathogen Vibrio parahaemolyticus poses a severe health hazard to halobios and significantly impedes intensive mariculture. This study aimed to evaluate the potential application of gliding arc discharge plasma (GADP) to control the infection of Vibrio parahaemolyticus in mariculture. This study investigated the inactivation ability of GADP against Vibrio parahaemolyticus in artificial seawater (ASW), changes in the water quality of GADP-treated ASW, and possible inactivation mechanisms of GADP against Vibrio parahaemolyticus in ASW. The results indicate that GADP effectively inactivated Vibrio parahaemolyticus in ASW. As the volume of ASW increased, the time required for GADP sterilization also increased. However, the complete sterilization of 5000 mL of ASW containing Vibrio parahaemolyticus of approximately 1.0 × 104 CFU/mL was achieved within 20 min. Water quality tests of the GADP-treated ASW demonstrated that there were no significant changes in salinity or temperature when Vibrio parahaemolyticus (1.0 ×104 CFU/mL) was completely inactivated. In contrast to the acidification observed in plasma-activated water (PAW) in most studies, the pH of ASW did not decrease after treatment with GADP. The H2O2 concentration in the GADP-treated ASW decreased after post-treatment. The NO2-concentration in the GADP-treated ASW remained unchanged after post-treatment. Further analysis revealed that GADP induced oxidative stress in Vibrio parahaemolyticus, which increased cell membrane permeability and intracellular ROS levels of Vibrio parahaemolyticus. This study provides a viable solution for infection with the halophilic pathogen Vibrio parahaemolyticus and demonstrates the potential of GADP in mariculture.


Assuntos
Peróxido de Hidrogênio , Gases em Plasma , Água do Mar , Vibrio parahaemolyticus , Água do Mar/microbiologia , Gases em Plasma/farmacologia , Gases em Plasma/química , Peróxido de Hidrogênio/química , Esterilização/métodos
9.
Foods ; 13(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38890902

RESUMO

Vibrio parahaemolyticus can cause acute gastroenteritis, wound infections, and septicemia in humans. The overuse of antibiotics in aquaculture may lead to a high incidence of the multidrug-resistant (MDR) pathogen. Nevertheless, the genome evolution of V. parahaemolyticus in aquatic animals and the mechanism of its antibiotic tolerance remain to be further deciphered. Here, we investigated the molecular basis of the antibiotic tolerance of V. parahaemolyticus isolates (n = 3) originated from shellfish and crustaceans using comparative genomic and transcriptomic analyses. The genome sequences of the V. parahaemolyticus isolates were determined (5.0-5.3 Mb), and they contained 4709-5610 predicted protein-encoding genes, of which 823-1099 genes were of unknown functions. Comparative genomic analyses revealed a number of mobile genetic elements (MGEs, n = 69), antibiotic resistance-related genes (n = 7-9), and heavy metal tolerance-related genes (n = 2-4). The V. parahaemolyticus isolates were resistant to sub-lethal concentrations (sub-LCs) of ampicillin (AMP, 512 µg/mL), kanamycin (KAN, 64 µg/mL), and streptomycin (STR, 16 µg/mL) (p < 0.05). Comparative transcriptomic analyses revealed that there were significantly altered metabolic pathways elicited by the sub-LCs of the antibiotics (p < 0.05), suggesting the existence of multiple strategies for antibiotic tolerance in V. parahaemolyticus. The results of this study enriched the V. parahaemolyticus genome database and should be useful for controlling the MDR pathogen worldwide.

10.
PhytoKeys ; 242: 39-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774390

RESUMO

A novel monoraphid diatom species, Cocconeiscrisscrossis You, Yu, Kociolek & Wang, sp. nov. is examined and described from the Qingyi River and Maolan Nature Reserve of southern China. The morphological description is based on light microscopy and scanning electron microscopy observations and the new species is compared with similar taxa in this genus. The characteristics unique to Cocconeiscrisscrossissp. nov. include its central area extending irregularly to both sides, it having closed valvocopulae with heavily silicified fimbriate margins and poles of the valvocopulae have 'sword-shaped' siliceous extensions. These features differentiate this new species from others in the genus. This new species was found in alkaline waterbodies, including streams, waterfall and ponds. It was usually found as an epiphyte on the stones; however, it was present on other substrates such as mosses.

11.
Cancer Sci ; 115(6): 1881-1895, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38566554

RESUMO

Triple-negative breast cancer (TNBC) exhibits heightened aggressiveness compared with other breast cancer (BC) subtypes, with earlier relapse, a higher risk of distant metastasis, and a worse prognosis. Transcription factors play a pivotal role in various cancers. Here, we found that factor forkhead box M1 (FOXM1) expression was significantly higher in TNBC than in other BC subtypes and normal tissues. Combining the findings of Gene Ontology (GO) enrichment analysis and a series of experiments, we found that knockdown of the FOXM1 gene attenuated the ability of TNBC cells to proliferate and metastasize both in vivo and in vitro. In addition, Spearman's test showed that FOXM1 significantly correlated with glycolysis-related genes, especially centromere protein A (CENPA) in datasets (GSE76250, GSE76124, GSE206912, and GSE103091). The effect of silencing FOXM1 on the inhibition of CENPA expression, TNBC proliferation, migration, and glycolysis could be recovered by overexpression of CENPA. According to MeRIP, the level of m6A modification on FOMX1 decreased in cells treated with cycloleucine (a m6A inhibitor) compared with that in the control group. The increase in FOXM1 expression caused by YTHDC1 overexpression could be reversed by the m6A inhibitor, which indicated that YTHDC1 enhanced FOXM1 expression depending on m6A modification. Therefore, we concluded that the YTHDC1-m6A modification/FOXM1/CENPA axis plays an important role in TNBC progression and glycolysis.


Assuntos
Proliferação de Células , Progressão da Doença , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Glicólise , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Humanos , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Camundongos Nus , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
12.
Mol Immunol ; 168: 64-74, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428216

RESUMO

Septic lung injury is characterized by uncontrollable inflammatory infiltrations and acute onset bilateral hypoxemia. Evidence has emerged of the beneficial effect of hydrogen in acute lung injury (ALI), but the underlying mechanism is unclear. In this research, the recovery action of hydrogen on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells was investigated. The 7-day survival rate and body weight of mice were measured after intraperitoneal injection of LPS. Lung function was determined by a whole body plethysmography (WBP) system using the indicators respiratory rate and enhanced pause. Hematoxylin and eosin (HE) staining confirmed the signs of pulmonary edema and inflammatory ooze. Reverse transcription-polymerase chain reaction (RT-PCR) quantification was used to detect the expression of inflammatory factors. Western blotting analysis evaluated the expression levels of involved proteins in the AMP-activated protein kinase (AMPK) pathway. The experimental results confirmed that hydrogen provided an essential solution to the dissipative effects of LPS on survival rate, weight loss and lung function. The LPS-stimulated inflammatory factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also suppressed by hydrogen in A549 cells. Western blot analysis showed that hydrogen significantly upregulated the levels of phosphorylated AMPK (p-AMPK) and lowered the LPS-induced increased expression of dynamin-related protein 1 (Drp1) and Caspase3. These findings prove that hydrogen attenuated LPS-treated ALI by activating the AMPK pathway, supporting the feasibility of hydrogen treatment for sepsis.


Assuntos
Lesão Pulmonar Aguda , Endotoxinas , Animais , Camundongos , Endotoxinas/metabolismo , Lipopolissacarídeos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Hidrogênio/efeitos adversos , Hidrogênio/metabolismo , Transdução de Sinais , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Front Physiol ; 15: 1341287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523809

RESUMO

Thyroidectomy scars, located on the exposed site, can cause distress in patients. Owing to the cosmetic importance of thyroidectomy scars, many studies have been conducted on its prevention and treatment. Scar formation factors mainly include inflammatory cell infiltration, angiogenesis, fibroblast proliferation, secretion of cytokines such as transforming growth factor (TGF)-ß1, and mechanical tension on the wound edges. Anti-scar methods including topical anti-scar agents, skin tension-bearing devices, and local injections of botulinum toxin, as well as lasers and phototherapies, that target these scar formation factors have been developed. However, current studies remain fragmented, and there is a lack of a comprehensive evaluation of the impacts of these anti-scar methods on treating thyroidectomy scars. Early intervention is a crucial but often neglected key to control hyperplastic thyroidectomy scars. Therefore, we review the currently adopted early postoperative strategies for thyroidectomy scar reduction, aiming to illustrate the mechanism of these anti-scar methods and provide flexible and comprehensive treatment selections for clinical physicians to deal with thyroidectomy scars.

14.
Int Immunopharmacol ; 130: 111688, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38394886

RESUMO

Magnesium hydride (MgH2) is a hydrogen storage material that is known for its high capacity and safety and is capable of releasing hydrogen in a controlled manner when administered orally. This release of hydrogen has been associated with a range of biological effects, including anti-inflammatory properties, antioxidant activity, and protection of the intestinal barrier. Previous research has shown that neutrophil extracellular traps (NETs) play a role in the dysfunction of the intestinal barrier in conditions such as sepsis and critical illnesses. However, it remains unclear as to whether MgH2 can protect the intestinal barrier by inhibiting NET formation, and the underlying mechanisms have yet to be elucidated. A rat model of hemorrhagic shock was created, and pretreatment or posttreatment procedures with MgH2 were performed. After 24 h, samples from the small intestine and blood were collected for analysis. In vitro, human neutrophils were incubated with either phorbol-12-myristate-13-acetate (PMA) or MgH2. Reactive oxygen species generation and the expression of key proteins were assessed. The results demonstrated that MgH2 administration led to a decrease in inflammatory cytokines in the serum and mitigated distant organ dysfunction in rats with HS. Furthermore, MgH2 treatment reversed histopathological damage in the intestines, improved intestinal permeability, and enhanced the expression of tight junction proteins (TJPs) during HS. Additionally, MgH2 treatment was found to suppress NET formation in the intestines. In vitro pretreatment with MgH2 alleviated intestinal monolayer barrier disruption that was induced by NETs. Mechanistically, MgH2 pretreatment reduced ROS production and NET formation, inhibited the activation of ERK and p38, and suppressed the expression of the PAD4 protein. These findings indicated that MgH2 may inhibit NET formation in a ROS/MAPK/PAD4-dependent manner, which reduces NET-related intestinal barrier damage, thus offering a novel protective role in preventing intestinal barrier dysfunction during HS.


Assuntos
Armadilhas Extracelulares , Enteropatias , Choque Hemorrágico , Humanos , Ratos , Animais , Choque Hemorrágico/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Magnésio/uso terapêutico , Magnésio/metabolismo , Magnésio/farmacologia , Neutrófilos , Enteropatias/metabolismo , Hidrogênio/farmacologia
16.
Small ; : e2307985, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084466

RESUMO

Genetic variations are always related to human diseases or susceptibility to therapies. Nucleic acid probes that precisely distinguish closely related sequences become an indispensable requisite both in research and clinical applications. Here, a Sequence-guided DNA LOCalization for leaKless DNA detection (SeqLOCK) is introduced as a technique for DNA hybridization, where the intended targets carrying distinct "guiding sequences" act selectively on the probes. In silicon modeling, experimental results reveal considerable agreement (R2  = 0.9228) that SeqLOCK is capable of preserving high discrimination capacity at an extraordinarily wide range of target concentrations. Furthermore, SeqLOCK reveals high robustness to various solution conditions and can be directly adapted to nucleic acid amplification techniques (e.g., polymerase chain reaction) without the need for laborious pre-treatments. Benefiting from the low hybridization leakage of SeqLOCK, three distinct variations with a clinically relevant mutation frequency under the background of genomic DNA can be discriminated simultaneously. This work establishes a reliable nucleic acid hybridization strategy that offers great potential for constructing robust and programmable systems for molecular sensing and computing.

17.
Front Microbiol ; 14: 1294177, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954246

RESUMO

Vibrio cholerae is a common waterborne pathogen that can cause pandemic cholera in humans. The bacterium with heavy metal-tolerant phenotypes is frequently isolated from aquatic products, however, its tolerance mechanisms remain unclear. In this study, we investigated for the first time the response of such V. cholerae isolates (n = 3) toward the heavy metal (Cd2+, Ni2+, Pb2+, and Zn2+) stresses by comparative secretomic and proteomic analyses. The results showed that sublethal concentrations of the Pb2+ (200 µg/mL), Cd2+ (12.5 µg/mL), and Zn2+ (50 µg/mL) stresses for 2 h significantly decreased the bacterial cell membrane fluidity, but increased cell surface hydrophobicity and inner membrane permeability, whereas the Ni2+ (50 µg/mL) stress increased cell membrane fluidity (p < 0.05). The comparative secretomic and proteomic analysis revealed differentially expressed extracellular and intracellular proteins involved in common metabolic pathways in the V. cholerae isolates to reduce cytotoxicity of the heavy metal stresses, such as biosorption, transportation and effluxing, extracellular sequestration, and intracellular antioxidative defense. Meanwhile, different defensive strategies were also found in the V. cholerae isolates to cope with different heavy metal damage. Remarkably, a number of putative virulence and resistance-associated proteins were produced and/or secreted by the V. cholerae isolates under the heavy metal stresses, suggesting an increased health risk in the aquatic products.

18.
Int J Biol Sci ; 19(16): 5204-5217, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928267

RESUMO

Circulating tumor cells (CTCs) are cells that detach from the primary tumor and enter the bloodstream, playing a crucial role in the metastasis of lung cancer. Unfortunately, there is currently a lack of drugs specifically designed to target CTCs and prevent tumor metastasis. In this study, we present evidence that polyphyllin VII, a potent anticancer compound, effectively inhibits the metastasis of lung cancer by inducing a process called anoikis in CTCs. We observed that polyphyllin VII had significant cytotoxicity and inhibited colony formation, migration, and invasion in both our newly established cell line CTC-TJH-01 and a commercial lung cancer cell line H1975. Furthermore, we found that polyphyllin VII induced anoikis and downregulated the TrkB and EGFR-MEK/ERK signaling pathways. Moreover, activation of TrkB protein did not reverse the inhibitory effect of polyphyllin VII on CTCs, while upregulation of EGFR protein effectively reversed it. Furthermore, our immunodeficient mouse models recapitulated that polyphyllin VII inhibited lung metastasis, which was associated with downregulation of the EGFR protein, and reduced the number of CTCs disseminated into the lungs by inducing anoikis. Together, these results suggest that polyphyllin VII may be a promising compound for the treatment of lung cancer metastasis by targeting CTCs.


Assuntos
Neoplasias Pulmonares , Animais , Camundongos , Anoikis , Linhagem Celular Tumoral , Receptores ErbB/genética , Neoplasias Pulmonares/metabolismo , Metástase Neoplásica , Humanos
19.
Molecules ; 28(19)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37836639

RESUMO

Curcumin possesses a wide spectrum of liver cancer inhibition effects, yet it has chemical instability and poor metabolic properties as a drug candidate. To alleviate these problems, a series of new mono-carbonyl curcumin derivatives G1-G7 were designed, synthesized, and evaluated by in vitro and in vivo studies. Compound G2 was found to be the most potent derivative (IC50 = 15.39 µM) compared to curcumin (IC50 = 40.56 µM) by anti-proliferation assay. Subsequently, molecular docking, wound healing, transwell, JC-1 staining, and Western blotting experiments were performed, and it was found that compound G2 could suppress cell migration and induce cell apoptosis by inhibiting the phosphorylation of AKT and affecting the expression of apoptosis-related proteins. Moreover, the HepG2 cell xenograft model and H&E staining results confirmed that compound G2 was more effective than curcumin in inhibiting tumor growth. Hence, G2 is a promising leading compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , Curcumina/química , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Antineoplásicos/química , Simulação de Acoplamento Molecular , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Proliferação de Células , Apoptose , Linhagem Celular Tumoral
20.
J Clin Lab Anal ; 37(15-16): e24956, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37661301

RESUMO

BACKGROUND: Sampling and testing for SARS-CoV-2 is a widely recognized method for identifying patients with COVID-19. However, there is limited research available on the stability of nucleic acids in viral storage solutions. METHODS: This paper investigates the components that provide better protection for virus and nucleic acid detection. The study utilized real-time quantitative fluorescent PCR to detect SARS-CoV-2 and evaluate the preservation effect and stability of SARS-CoV-2 viral storage solution under various conditions, including different guanidinium salts, brands, and storage conditions. RESULTS: All brands of inactivated virus preservation solutions demonstrated effective preservation and stability. However, 0.5 mol/L guanidine hydrochloride and guanidine isothiocyanate solutions exhibited poor antiseptic effects. Additionally, refrigerated storage showed better preservation compared to room temperature storage. CONCLUSIONS: We recommend using inactivated virus collection solution to preserve and transport samples and testing preferably within 6 hours to reduce false negatives of NAT results.

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