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1.
Small ; 20(20): e2306909, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38100246

RESUMEN

Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi-drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus-penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near-infrared photosensitizer T780T-Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light-induced anti-H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T-Gu releasing to target the H. pylori surface and ablate multi-drug resistant (MDR) H. pylori. In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori. The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Moco , Helicobacter pylori/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Moco/metabolismo , Animales , Fototerapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Glucolípidos/química , Glucolípidos/farmacología , Ratones , Administración Oral
2.
J Am Chem Soc ; 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37023253

RESUMEN

Glucose, a critical source of energy, directly determines the homeostasis of the human body. However, due to the lack of robust imaging probes, the mechanism underlying the changes of glucose homeostasis in the human body remains unclear. Herein, diboronic acid probes with good biocompatibility and high sensitivity were synthesized based on an ortho-aminomethylphenylboronic acid probe, phenyl(di)boronic acid (PDBA). Significantly, by introducing the water-solubilizing group -CN directly opposite the boronic acid group and -COOCH3 or -COOH groups to the ß site of the anthracene in PDBA, we obtained the water-soluble probe Mc-CDBA with sensitive response (F/F0 = 47.8, detection limit (LOD) = 1.37 µM) and Ca-CDBA with the highest affinity for glucose (Ka = 4.5 × 103 M-1). On this basis, Mc-CDBA was used to identify glucose heterogeneity between normal and tumor cells. Finally, Mc-CDBA and Ca-CDBA were used for imaging glucose in zebrafish. Our research provides a new strategy for designing efficient boronic acid glucose probes and powerful new tools for the evaluation of glucose-related diseases.

3.
Small ; 19(4): e2205248, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36417577

RESUMEN

Helicobacter pylori (H. pylori) infection has been the leading cause of gastric cancer development. In recent years, the resistance of H. pylori against antibiotic treatment has been a great challenge for most countries worldwide. Since biofilm formation is one of the reasons for the antibiotic resistance of H. pylori, and phototherapy has emerged as a promisingly alternative antibacterial treatment, herein the bacteria-targeted near-infrared (NIR) photosensitizer (T780T-Gu) by combining positively-charged guanidinium (Gu) with an efficient phototherapeutic agent T780T is developed. The proposed molecule T780T-Gu exhibits synergistic photothermal therapy/photodynamic therapy effect against both H. pylori biofilms and multidrug-resistant (MDR) clinical strains. More importantly, the phototherapy mechanism of T780T-Gu acquired by the RNA-seq analysis indicates that structural deficiency as well as a decrease in metabolism and defense activity are the possible reasons for the efficient H. pylori phototherapy.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fototerapia , Biopelículas , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
4.
Ann Hematol ; 102(12): 3555-3566, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37770617

RESUMEN

Growing evidence suggests that highly intestinal microbiota diversity modulates host inflammation and promotes immune tolerance. Several studies have reported that patients undergoing allo-HSCT have experienced microbiota disruption that is characterized by expansion of potentially pathogenic bacteria and loss of microbiota diversity. Thus, the primary aim of this meta-analysis was to determine the association of intestinal microbiota diversity and outcomes after allo-HSCT, and the secondary aim was to analyze the associations of some specific microbiota abundances with the outcomes of allo-HSCT. Electronic databases of Pubmed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2023, and 17 studies were found eligible. The pooled estimate suggested that higher intestinal microbiota diversity was significantly associated with overall survival (OS) benefit (HR = 0.66, 95% CI: 0.55-0.78), as well as decreased risk of transplant-related mortality (HR = 0.56, 95% CI: 0.41-0.76), and lower incidence of grade II-IV aGVHD (HR = 0.41, 95% CI: 0.27-0.63). Furthermore, higher abundance of Clostridiales was associated with a superior OS (HR = 0.40, 95% CI: 0.18-0.87), while higher abundance of Enterococcus (HR = 2.03, 95% CI: 1.55-2.65), γ-proteobacteria (HR = 2.82, 95% CI: 1.53-5.20), and Candida (HR = 3.80, 95% CI: 1.32-10.94) was an adverse prognostic factor for OS. Overall, this meta-analysis highlights the protective role of higher intestinal microbiota diversity on outcomes after allo-HSCT during both pre-transplant and post-transplant periods. Some specific microbiota can be useful in the identification of patients at risk of mortality, offering new tools for individualized pre-emptive or therapeutic strategies to improve allo-HSCT outcomes.


Asunto(s)
Microbioma Gastrointestinal , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Microbiota , Humanos , Recurrencia Local de Neoplasia/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Bacterias , Enfermedad Injerto contra Huésped/etiología
5.
Anal Chem ; 94(49): 17160-17168, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36445943

RESUMEN

Recently, nanoformulations have been widely applied in the delivery of organic photothermal agents (OPTAs) for cancer therapy to prolong blood circulation or improve tumor-targeting capacity. However, the systematic evaluations of their effects on the photothermal behavior of OPTAs are limited, especially for different types of nanoparticle systems. Herein, we prepared two kinds of nanoparticles (BSA and PEG nanoparticles (NPs)) to load an OPTA, a cyanine photosensitizer (IR780-O-TPE), and investigated their photothermal response, organelle targeting, and in vivo therapeutic efficacy. Due to different assembly forms, the two NPs showed distinct morphological changes after exposure to laser or hyperthermia. Under laser irradiation at 808 nm, BSA NPs could release IR780-O-TPE more efficiently than PEG NPs. We speculate that this phenomenon is probably caused by dual-responsive release of IR780-O-TPE from BSA NPs against light and hyperthermia. Moreover, IR780-O-TPE/BSA NPs were highly mitochondria-targeting and therefore displayed significant inhibition of cell viability. In contrast, IR780-O-TPE/PEG NPs were "shell-core" nanostructures and more stable under laser stimulation. As a consequence, the mitochondria-targeting and anticancer photothermal therapy by IR780-O-TPE/PEG NPs was less obvious. This study revealed the significance of nanocarrier design for OPTA delivery and demonstrated that BSA NPs could release IR780-O-TPE more effectively for efficient photothermal therapy. We also believe that the dual-responsive release of OPTAs from NPs can provide an effective strategy to promote anticancer photothermal treatment.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Nanoestructuras , Neoplasias , Humanos , Fototerapia , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral
6.
Ren Fail ; 44(1): 1486-1497, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36000917

RESUMEN

BACKGROUND: Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. METHODS: The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. RESULTS: We found that pPENK [OR 1.093 (95% CI 1.022-1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831-0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003-1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874-0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000-1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997-1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. CONCLUSIONS: The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.


Asunto(s)
Síndrome Cardiorrenal , Insuficiencia Cardíaca , Biomarcadores , Síndrome Cardiorrenal/diagnóstico , Diagnóstico Precoz , Encefalinas , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Humanos , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Pronóstico , Estudios Prospectivos , Precursores de Proteínas
7.
J Am Chem Soc ; 143(49): 20828-20836, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34860505

RESUMEN

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.


Asunto(s)
Antineoplásicos/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Indoles/uso terapéutico , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Estilbenos/uso terapéutico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/efectos de la radiación , Humanos , Indoles/síntesis química , Indoles/efectos de la radiación , Rayos Infrarrojos , Ratones Endogámicos BALB C , Neoplasias/diagnóstico por imagen , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/efectos de la radiación , Terapia Fototérmica , Estilbenos/síntesis química , Estilbenos/efectos de la radiación
10.
Food Chem ; 440: 138194, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38104447

RESUMEN

The effects of apple fiber on gluten structure and corresponding frozen dough quality during frozen storage were studied. The addition of 0.50% and 0.75% apple fiber effectively preserved gluten structure by inhibiting the breakage of disulfide bonds and promoting the formation of hydrogen bonds. Notably, the presence of 0.75% apple fiber increased the ß-turn of gluten from 29.60% to 33.84%. Fiber-enriched frozen dough exhibited a smoother and more compact microstructure, but excessive fiber addition (more than 1.00%) had adverse effects. The freezable water content of frozen dough decreased as fiber addition increased. Correspondingly, the addition of 1.50% apple fiber resulted in a 56.08% increase in storage modulus, indicating improved viscoelasticity of the dough. Consequently, the addition of 0.50% and 0.75% apple fiber alleviated the quality deterioration of frozen dough bread in terms of larger specific volume, softer and more uniform crumb.


Asunto(s)
Malus , Glútenes/química , Viscosidad , Fibras de la Dieta , Pan
11.
Int J Biol Macromol ; 270(Pt 2): 132049, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38704060

RESUMEN

In this study, we examined the possibility of using industrial microwave processing to enhance the gelling properties and reduce the starch digestibility of mung bean flour (MBF). MBF (12.6 % moisture) was microwaved at a power of 6 W/g to different final temperatures (100-130 °C), and then its structural and functional properties were characterized. The microwave treatment had little impact on the crystalline structure or amylose content of the starch, but it roughened the starch granule surfaces and decreased the short-range ordered structure and degree of branching. In addition, the extent of mung bean protein denaturation caused by the microwave treatment depended on the final temperature. Slightly denaturing the proteins (100 °C) did not affect the nature of the gels (protein phase dispersed in a starch phase) but the gel network became more compact. Moderately denaturing the proteins (110-120 °C) led to more compact and homogeneous starch-protein double network gels. Excessive protein denaturation (130 °C) caused the gel structure to become more heterogeneous. As a result, the facilitated tangles between starch chains by more linear starch molecules after debranching, and the protein network produced by moderate protein denaturation led to the formation of stronger gel and the improvement of plasticity during large deformation (large amplitude oscillatory shear-LAOS). Starch recrystallization, lipid complexion, and protein network retard starch digestion in the MBF gels. In conclusion, an industrial microwave treatment improved the gelling and digestive properties of MBF, and Lissajous curve has good adaptability in characterizing the viscoelasticity of gels under large deformations.


Asunto(s)
Harina , Geles , Microondas , Desnaturalización Proteica , Reología , Almidón , Vigna , Almidón/química , Vigna/química , Geles/química , Proteínas de Plantas/química , Temperatura , Amilosa/química
12.
ACS Appl Mater Interfaces ; 16(10): 12310-12320, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38412031

RESUMEN

Pyroptosis has been reported to improve the antitumor effect by evoking a more intense immune response and a therapeutic effect. For phototherapy, several photosensitizers have been found to initiate pyroptosis. However, the effect of pyroptosis associated with apoptosis in enhancing the antitumor therapy needs sufficient characterization, especially under long-term treatment. As a NIR photosensitizer, heptamethine cyanines have been discovered for anticancer phototherapy for deep tissue penetration and inherent tumor-targeted capability. However, they are not quite stable for long-term performance. To investigate the effect of pyroptosis along with apoptosis on the anticancer immune responses and phototherapy, here, we chemically modulate the cyanine IR780 to regulate hydrophobicity, stability, and intracellular targeting. Two photosensitizers, T780T-TPP and T780T-TPP-C12, were finally optimized and showed excellent photostability with high photothermal conversion efficiency. Although the cellular uptake of the two molecules was both mediated by OATP transporters, T780T-TPP induced tumor cell death via pyroptosis and apoptosis and accumulated in tumor accumulation, while T780T-TPP-C12 was prone to accumulate in the liver. Ultimately, via one injection-multiple irradiation treatment protocol, T780T-TPP displayed a significant antitumor effect, even against the growth of large tumors (200 mm3).


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Piroptosis , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fototerapia/métodos , Neoplasias/tratamiento farmacológico , Apoptosis , Mitocondrias , Nanopartículas/química , Línea Celular Tumoral
13.
Leuk Lymphoma ; 64(10): 1681-1688, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37424322

RESUMEN

The pathogenesis of donor cell leukemia (DCL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear and likely multifactorial. Leukemic transformation of healthy donor HSCs in recipient's bone marrow microenvironment provides a useful in vivo model for investigating the mechanisms involved in leukemogenesis. Here, we report a rare case of late-onset DCL developing in a recipient. Whole-genome sequencing indicates that donor-derived cells harboring clonal hematopoiesis of indeterminate potential (CHIP)-associated genetic alterations expand and eventually transform to full-blown AML via acquisition of additional somatic mutations within the recipient's bone marrow microenvironment. The 10× single-cell RNA sequencing reveals the abundance of GMP-like cells with a specific transcriptional signature in DCL. Moreover, impaired immune surveillance, including dysfunction of cytotoxic T lymphocytes (CTLs) and decreased number of canonical NK cells, is discovered in DCL. Our data add valuable information to the current understanding of the mechanisms of DCL.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia/genética , Genómica , Evolución Clonal/genética , Perfilación de la Expresión Génica , Microambiente Tumoral
14.
Medicine (Baltimore) ; 102(16): e33661, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37083765

RESUMEN

BACKGROUND: The improvement of oxygenation and pulmonary mechanics in patients under general anesthesia can be achieved by dexmedetomidine (DEX) infusion. However, its role in patients undergoing lateral supine shoulder arthroscopy has not been thoroughly studied. This study aimed to evaluate the effect of DEX on lung compliance in patients undergoing shoulder arthroscopic surgery in a lateral decubitus position. METHODS: The patients who underwent lateral recumbent shoulder arthroscopy under general anesthesia were randomly divided into the DEX group (group D) and the control group (group N). At the start of the trial, group D was given 0.5 µg/kg/hours continuous pumping until 30 minutes before the end of anesthesia; Group N was injected with normal saline at the same volume. The patients were recorded at each time point after intubation: supine position for 5 minutes (T0), lateral position for 5 minutes (T1), lateral position for 1 hour (T2), lateral position for 2 hours (T3), airway peak pressure, platform pressure, dynamic lung compliance, and static lung compliance, etc. RESULTS: At the end of the drug infusion, the DEX group showed significant improved pulmonary mechanics and higher lung compliance than the control group. Compared with group N, group D's heart rate and mean arterial pressure were lower at all time points; there was no statistical difference in Tidal volume and Pressure end-tidal carbon dioxide data at each time point in Group D. CONCLUSION: DEX can improve lung compliance and reduce airway pressure and platform pressure of patients undergoing shoulder arthroscopy in the lateral position under general anesthesia.


Asunto(s)
Dexmedetomidina , Humanos , Rendimiento Pulmonar , Dexmedetomidina/uso terapéutico , Hombro/cirugía , Artroscopía , Pulmón/cirugía
15.
Plant Physiol Biochem ; 205: 108189, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37979575

RESUMEN

Selenite is widely used to increase Selenium (Se) content in cereals, however excessive selenite may be toxic to plant growth. In this study, barley was malted to elucidate the action mechanism of selenite in the generation and detoxification of oxidative toxicity. The results showed that high doses (600 µM) of selenite radically increased oxidative stress by the elevated accumulation of superoxide and malondialdehyde, leading to phenotypic symptoms of selenite-induced toxicity like stunted growth. Barley tolerates selenite through a combination of mechanisms, including altering Se distribution in barley, accelerating Se efflux, and increasing the activity of some essential antioxidant enzymes. Low doses (150 µM) of selenite improved barley biomass, respiratory rate, root vigor, and maintained the steady-state equilibrium between reactive oxygen species (ROS) and antioxidant enzyme. Selenite-induced proline may act as a biosignal to mediate the response of barley to Se stress. Furthermore, low doses of selenite increased the glutathione (GSH) and ascorbate (AsA) concentrations by mediating the ascorbate-glutathione cycle (AsA-GSH cycle). GSH intervention and dimethyl selenide volatilization appear to be the primary mechanisms of selenite tolerance in barley. Thus, results from this study will provide a better understanding of the mechanisms of selenite tolerance in crops.


Asunto(s)
Hordeum , Selenio , Antioxidantes/metabolismo , Selenio/farmacología , Selenio/metabolismo , Hordeum/metabolismo , Germinación , Ácido Selenioso/farmacología , Glutatión/metabolismo , Estrés Oxidativo
16.
Neuropsychiatr Dis Treat ; 19: 329-336, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36778531

RESUMEN

Objective: To study the correlation between the adenosine triphosphate (ATP) content in the hippocampus of rats and delayed encephalopathy after acute carbon monoxide (CO) poisoning. Methods: A total of 40 male Wistar rats weighing 180-230g, in accordance with the random number table, were selected and divided into the delayed encephalopathy after acute carbon monoxide poisoning (DEACMP: Rats with cognitive impairment after carbon monoxide poisoning) group (n = 32) and the control group (n = 8). A DEACMP rat model was generated by inhalation of CO. The Morris water maze evaluated the ability to learn and memorize in rats. The changes in neurons in the hippocampus of the rats were observed by hematoxylin-eosin (HE) staining. Lastly, the ATP content in the hippocampus of the rats was measured by high-performance liquid chromatography (HPLC). Results: The ATP content of the experimental group was significantly higher than that of the control group in the hippocampus of the rat model, so the difference was statistically significant (P < 0.05); the intra-group comparison was made for the ATP content in the experimental group, and the difference was statistically significant as group 21d > group 14d > group 7d (P < 0.05); and no significant difference was found between group 21d and group 28d (P > 0.05). Conclusion: The changes in the ATP content in the hippocampus of the rats are correlated with the occurrence of delayed encephalopathy after acute carbon monoxide poisoning; it may take part in the pathogenesis of DEACMP. This offers some elicitation to the prevention and treatment of the disease.

17.
ACS Appl Mater Interfaces ; 15(22): 26252-26262, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37218741

RESUMEN

Low-temperature photothermal therapy (PTT) has the advantage of causing less damage to normal tissues and has attracted great attention in recent years. However, the efficacy of low-temperature PTT is restricted by the overexpression of heat shock proteins (HSPs), specifically HSP70 and HSP90. Inhibiting the function of these HSPs is a major strategy used in the development of new cancer therapies. Herein, we designed four T780T-containing thermosensitive nanoparticles to interrupt the energy supply for HSP expression using their TPP-based mitochondrial targeting action. The reversal behavior of the nanoparticles on the gambogic acid (GA)-induced compensatory increase of HSP70 was investigated in vitro by Western blot and in vivo by immunohistochemistry. The in vivo anticancer efficacy of the low-temperature PTT based on these thermosensitive nanoparticles was also systematically examined. The design proposes for the first time to utilize and elucidate the mechanism of the mitochondrial targeting of T780T-containing NPs in synergy with the HSP90 inhibition of GA to achieve an effective low-temperature PTT. This work not only provides a novel pathway for the dual inhibition of HSP70 and HSP90 but also opens up a new approach for low-temperature PTT of tumors.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Temperatura , Frío , Neoplasias/terapia , Mitocondrias , Fototerapia , Línea Celular Tumoral
18.
Clin Cosmet Investig Dermatol ; 16: 2737-2748, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37799505

RESUMEN

Carvajal syndrome is a rare hereditary cardiocutaneous syndrome caused by the variants of the desmoplakin (DSP) gene. In this study, we report a patient of Carvajal syndrome with a novel homozygous missense variant of DSP gene. We diagnosed a 7-year-old female patient with Carvajal syndrome characterized by dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia, who disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene found for the first time. Both her parents were heterozygous for the identified nonsense variant c.4597C > T (p.Q1533X) in DSP gene but neither showed evidence of Carvajal syndrome, indicating that this novel variant causes the disease in an autosomal recessive manner. Genotypes of Carvajal syndrome are even broader than so far anticipated. When patients with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia are found in clinical practice, Carvajal syndrome should be highly suspected, and family gene sequencing should be actively carried out.

19.
Talanta ; 256: 124260, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36640706

RESUMEN

Helicobacter pylori (H. pylori) infection has increasingly been a serious problem worldwide. The H. pylori infection can result in a series of stomach diseases including gastric carcinoma. There are two specific virulence genes (cagA and vacA) of H. pylori that are closely related to the occurrence of gastric cancer, and the common molecular detection methods (PCR, qPCR) are not suitable for high-screening test due to the requirement of expensive instruments and well-trained personals. Herein, we develop a rapid visual assay based on loop-mediated isothermal amplification (LAMP) for detecting H. pylori and its major virulence genes (cagA, vacAs1 and vacAm1) to guide clinical treatment for H. pylori infection. In this research, a fluorescent LAMP assay was established by optimizing the indicator of MnCl2-Calcein, so that the resulted color and fluorescence changes could be utilized to perform the visual detection for H. pylori and its virulence genes with high sensitivity (10-3 ng/µL). The proposed LAMP assay is simple, fast (30 min) and capable in providing more sensitive results than traditional methods in the test of 46 clinical biopsy samples. By detecting the three virulence genes together, we can profile the infection risk of the patients, and discuss the correlation among the genes. Moreover, the method could be used to diagnose virulently infected individuals and benefit the eradication of H. pylori in early warning for gastric cancer.


Asunto(s)
Carcinoma , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Virulencia/genética , Proteínas Bacterianas/genética , Antígenos Bacterianos/genética , Helicobacter pylori/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Genotipo , Gastritis/genética , Gastritis/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/patología
20.
Medicine (Baltimore) ; 101(45): e31569, 2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36397349

RESUMEN

Sevoflurane and desflurane are commonly used inhalation anesthetics in clinical practice. This study compared the synergistic effects of sevoflurane and desflurane on the muscarinic agent vecuronium in laparoscopic colon cancer surgery. The aim of this study was to compare sevoflurane and desflurane in a synergistic effect on the muscle relaxant vecuronium in laparoscopic colon cancer surgery. Sixty patients undergoing elective laparoscopic radical resection of colon cancer were randomly divided into sevoflurane (n = 30) and desflurane (n = 30) groups. After anesthesia and successful tracheal intubation, patients in both groups were maintained with combined remifentanil. Muscle relaxant effects were monitored in both groups using a muscle relaxant monitor (train of stimuli-Watch), the onset time, T1 and T2 recovery time, and muscle relaxant dosage of vecuronium were observed. Hemodynamic changes were observed in both groups, and the dosage of vasoactive drugs was recorded. The quality of recovery of the patients was evaluated using the Mini-Mental State Examination (MMSE) and the discharge from the Aldrete score criteria. There was no significant difference in the onset time of vecuronium between the two groups (P > .05). The desflurane group's T1 and T2 recovery times were later than that of the sevoflurane group. The dosage of vecuronium was statistically significantly less than that in the sevoflurane group (P < .05); the extubation time in the desflurane group was statistically significantly longer than that in the sevoflurane group (P < .05). There were no significant differences in preoperative and intraoperative mean arterial pressure, heart rate, ephedrine and atropine dosage, MMSE score, and Aldrete score between the 2 groups (P > .05). Compared with sevoflurane, desflurane has a stronger synergistic effect on the muscle relaxant of vecuronium without increasing the incidence of cardiovascular adverse reactions and affecting patient recovery.


Asunto(s)
Neoplasias del Colon , Isoflurano , Laparoscopía , Éteres Metílicos , Humanos , Sevoflurano/farmacología , Desflurano , Bromuro de Vecuronio , Éteres Metílicos/efectos adversos , Periodo de Recuperación de la Anestesia , Neoplasias del Colon/cirugía , Músculos
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