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1.
Int J Food Microbiol ; 385: 109998, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36371998

RESUMO

Nutrients on produce surfaces are vital for successful enteric pathogen colonisation. In this study, we investigated natural variation in metabolite profiles of Romaine 'Parris Island Cos' and red oak-leaf lettuce 'Mascara' under regular and restricted watering conditions. We also investigated the impact of plant drought stress on the Salmonella - lettuce association. Salmonella Newport and Typhimurium were able to persist at higher levels on regularly watered Romaine than red oak-leaf lettuce. Drought treatment to lettuce impaired epiphytic Salmonella association, with S. Newport and Typhimurium being differentially affected. A higher log reduction of both serotypes was measured on drought-subjected red oak-leaf lettuce plants than controls, but S. Typhimurium was unaffected on water deficit-treated Romaine lettuce (p < 0.05). To assess Salmonella interaction with leaf surface metabolites, leaf washes collected from both cultivars were inoculated and found to be able to support S. Newport growth, with higher levels of Salmonella retrieved from Romaine washes (p < 0.05). The lag phase of S. Newport in washes from water restricted red oak-leaf lettuce was prolonged in relation to regularly-watered controls (p < 0.05). Untargeted plant metabolite profiling using electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) revealed natural variation between Romaine and red oak-leaf lettuce profiles for leaf tissue and leaf washes. Metabolite profile shifts were detected in both lettuce types in response to drought stress, but more unique peaks were detected in red oak-leaf than Romaine lettuce after drought treatment. Variation between the two cultivars was in part attributed to naturally higher levels of flavonoids and anthocyanins in red oak-leaf lettuce compared to Romaine. Moreover, red oak-leaf, but not Romaine lettuce, responded to drought by inducing the accumulation of proline, phenolics, flavonoids and anthocyanins. Drought stress, therefore, enhanced the functional food properties of red oak-leaf lettuce. Salmonella growth dynamics in lettuce leaf washes suggested that natural variation and drought-induced changes in metabolite profiles in lettuce could partly explain the differential susceptibility of various lettuce types to Salmonella, although the primary or secondary metabolites mediating this effect remain unknown. Regulated mild water stress should be investigated as an approach to lower Salmonella contamination risk in suitable lettuce cultivars, while simultaneously boosting the health beneficial quality of lettuce.

2.
J Pharm Biomed Anal ; 223: 115128, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36327582

RESUMO

Oleum Cinnamomi is the essential oil obtained from the herb Fructus Cinnamomi which is used by the Hmong people in traditional medicine for the treatment of various diseases. At present, there are a variety of marketed preparations with it as the main medicine on the market. Information regarding the in vivo process of it is lacking, which has become a bottleneck restricting its development and utilization. In view of this, a GC-MS SIM analysis method was established for the simultaneous determination of six main volatile components [eucalyptol, p-cymene, 4-carvomenthenol, 4-isopropyl-2-cyclohexenone, α-terpineol, and 2-(4-Methylphenyl)-propan-2-ol] in plasma and ten tissues of rats to study their pharmacokinetic and distribution characteristics in vivo. The pharmacokinetic results showed that the t1/2 of each index was 0.41-1.66 h, Tmax was 0.16-0.68 h, Cmax was 13.66-2015.02 ng/mL, AUC0-t was 12.84-4299.00 h·ng/mL, CLZ/F was 1750.93-107013.11 mL/h/kg. This meant that the six components could be absorbed quickly, had a short residence time, and be eliminated quickly in the body. Among them, eucalyptol has the highest degree of absorption and a larger amount of entering the body. Moreover, the Cmax and AUC0-t of the six components increased correspondingly with the increase of the dose, indicating that the concentration of Oleum Cinnamomi in the rat plasma was dose-dependent. At different time points, the six components were widely distributed with uneven characteristics in the body. The six components mainly tend to be distributed in stomach, small intestine, and liver, followed by kidney, spleen, heart, and brain, and to a lesser extent in lung, skin, and muscle. And the six components were eliminated quickly in each tissue. The pharmacokinetic process and tissue distribution characteristics of Oleum Cinnamomi were expounded in this study, which can provide scientific theory for the in-depth development and guidance of clinical drug use of Oleum Cinnamomi, and at the same time provide a medicinal material basis for the in-depth development and utilization of Oleum Cinnamomi.

3.
Bioact Mater ; 20: 93-110, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35633874

RESUMO

The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to ∼1.0 MPa), elasticity (elongation ∼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.

4.
Neural Regen Res ; 18(2): 364-367, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900431

RESUMO

Therapeutic intervention for spinal cord injury is limited, with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative training. As compared with learning novel compensatory strategies, rehabilitation focuses on restoring movements lost to injury. Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning, or if it engages previously trained motor circuits without requiring novel learning remains an open question. In this study, mice were randomly assigned to receive intraperitoneal injection with the pan-nicotinic, non-competitive antagonist mecamylamine and the nicotinic α7 subunit selective antagonist methyllycaconitine citrate salt or vehicle (normal saline) prior to motor learning assays, then randomly reassigned after motor learning for rehabilitation study post-injury. Cervical spinal cord dorsal column lesion was used as a model of incomplete injury. Results of this study showed that nicotinic acetylcholine signaling was required for motor learning of the single pellet-reaching task but it was dispensable for the rehabilitation of the same task after injury. Our findings indicate that critical differences exist between the molecular mechanisms supporting compensatory motor learning strategies and the restoration of behavior lost to spinal cord injury.

5.
Front Neurol ; 13: 993979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388205

RESUMO

Background and objective: Gait disturbances are common in the elderly and can lead to the loss of functional independence and even death. Enlarged perivascular space (EPVS) and motor performance may be related, but only few studies have explored this relationship. The aim of our study was to investigate the effects of both the severity and location of EPVS on movement disorders. Method: Two hundred and six participants aged between 45 and 85 years old with complete magnetic resonance imaging (MRI) data were included in our analysis. EPVS were divided into basal ganglia (BG) and centrum semiovale (CSO), and their grades were measured. Gait was assessed quantitatively using a 4-m walkway and TUG test as well as semi-quantitatively using the Tinetti and SPPB tests. The function of upper extremities was evaluated by 10-repeat pronation-supination, 10-repeat finger-tapping, and 10-repeat opening and closing of the hands. Results: Both high-grade EPVS, whether in BG and CSO, were independently correlated with gait parameters, the TUG time, Tinetti, and SPPB tests. The EPVS located in BG had a significant association with 10-repeat finger-tapping time (ß = 0.231, P = 0.025) and a similar association was also observed between CSO-EPVS and 10-repeat pronation-supination time (ß = 0.228, P = 0.014). Conclusion: Our results indicated that EPVS was associated with gait disturbances, and a further investigation found that EPVS has an association with upper extremities disorder. EPVS should be considered as a potential target for delaying gait and upper extremities damage since CSVD can be prevented to some extent.

6.
Ann Transl Med ; 10(20): 1148, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388834

RESUMO

Background: Systemic lupus erythematosus (SLE) is a systemic disease, which can bring damage to multiple organ systems. It is easily misdiagnosed as mechanical intestinal obstruction and treated by surgery, which not only brings physical pain to patients, but also increases their economic burden. On the other hand, Castleman disease (CD) is also a rare disease that can be easily missed clinically. Consequently, IPO in SLE complicated by CD is extremely rare in clinical practice and easily ignored for clinicians, which may result in delayed diagnosis, and treatment, and even overtreatment. Case Description: An 18-year-old Chinese woman presented with over a month's history of abdominal pain and fever, accompanied by abdominal distension and nausea. The patient was admitted to a local hospital before admission, and imaging test showed intestinal obstruction. After symptomatic treatment, abdominal pain was relieved, but symptoms reappeared about 20 days later. In addition, a red rash on face, light-sensitiveness and alopecia appeared 7 months prior to presentation. Physical examination showed a temperature of 38.9 ℃, facial butterfly erythema, enlarged axillary lymph nodes, lower abdominal tenderness, and diminished bowel sounds. Laboratory examinations showed proteinuria, decreased white blood cell, low C3 and low C4, positive antinuclear antibody (ANA), and positive anti-double-stranded DNA (anti-dsDNA). Abdominal noncontrast computed tomography (CT) showed partial small bowel obstruction. Chest contrast-enhanced CT showed multiple enlarged lymph nodes in the bilateral axillary and mediastinal areas. The results of the axillary lymph node biopsy were consistent with the typical histologic features of clear vascular CD. After glucocorticoid and immunosuppression therapy, the patient's immune indexes and proteinuria gradually returned to normal and abdominal pain did not recur during the follow up. Conclusions: In order to avoid misdiagnosis of IPO in SLE and missed diagnosis of SLE complicated by CD, this case emphasizes the importance of medical history combined with appropriate laboratory examination, imaging examination and lymph node biopsy in SLE patients with lymphadenopathy for accurate diagnosis and reasonable treatment. At the same time, this case report aims to improve the diagnostic thinking of clinicians for similar patients.

7.
Front Microbiol ; 13: 1051730, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406410

RESUMO

Strawberry gray mold caused by Botrytis cinerea is one of the most severe diseases in pre- and post-harvest periods. Although fungicides have been an effective way to control this disease, they can cause serious "3R" problems (Resistance, Resurgence and Residue). In this study, Streptomyces sp. sdu1201 isolated from the hindgut of the fungus-growing termite Odontotermes formosanus revealed significant antifungal activity against B. cinerea. Four compounds (1-4) were isolated from Streptomyces sp. sdu1201 and further identified as actinomycins by the HRMS and 1D NMR data. Among them, actinomycin D had the strongest inhibitory activity against B. cinerea with the EC50 value of 7.65 µg mL-1. The control effect of actinomycin D on strawberry gray mold was also tested on fruits and leaves in vitro, and its control efficiency on leaves was 78.77% at 3 d. Moreover, actinomycin D can also inhibit the polarized growth of germ tubes of B. cinerea. Therefore, Streptomyces sp. sdu1201 and actinomycin D have great potential to gray mold as biocontrol agents.

8.
Front Cardiovasc Med ; 9: 1011037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407450

RESUMO

Background: Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation is an emerging one-stop hybrid procedure for non-valvular atrial fibrillation (AF). This study was performed to compare the efficacy and safety of the Watchman device vs. the LAmbre device for this combined procedure. Methods: Two hundred and thirty two patients with AF who underwent the combined procedure were enrolled and divided into two subgroups depending on the device choice: the Watchman-combined group (n = 118) and the LAmbre-combined group (n = 114). The periprocedural and follow-up adverse events in both groups were documented. Results: The mean CHA2DS2-VASc score and HAS-BLED score in the Watchman-combined group and LAmbre-combined group were 3.7 ± 1.5 vs. 3.8 ± 1.5 and 2.5 ± 1.1 vs. 2.3 ± 1.1, respectively (all P > 0.05). Successful LAAC was achieved in all patients. The rate of major periprocedural complications and AF recurrence at 6 months post-procedure were similar between the Watchman-combined group and LAmbre-combined group (0.8 vs. 0.9%, P = 1.00; 22.0 vs. 15.8%, P = 0.23). During 2.6 ±0 .7 vs.1.6 ± 1.6 years follow-up, the rate of major clinical adverse events, including stroke and major bleeding, were comparable between the Watchman-combined group and the LAmbre-combined group (2.6 vs. 1.1% per 100 patient-years, P = 0.33). The intraprocedural peri-device leakage (PDL) rate was similar between the Watchman-combined group and the LAmbre-combined group (5.1 vs. 6.1%, P = 0.73), but the PDL rate was significantly higher at 3-6 months transesophageal echocardiography (TEE) follow-up than the intraprocedural PDL rate in both groups (21.6 vs. 5.1%; 36.6 vs. 6.1%, respectively), with a more obvious increase in minimal PDL rate in the LAmbre-combined group than the Watchman-combined group (36.6 vs. 21.6%, P < 0.05). Conclusion: The Watchman and LAmbre devices were comparable in efficacy and safety for the combined procedure. The minimal PDL rate at short-term TEE follow-up was higher in the LAmbre-combined group than the Watchman-combined group.

9.
Univers Access Inf Soc ; : 1-14, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36407567

RESUMO

Education is one area that was significantly affected by the COVID-19 pandemic with much of the education being transferred online. Many subjects that require hands-on experimental experience suffer when taught online. Education is also one area that many believe can benefit from the advances in virtual reality (VR) technology, particularly for remote, online learning. Furthermore, because the technology shows overall good results with hands-on experiential learning education, one possible way to overcome online education barriers is with the use of VR applications. Given that VR has yet to make significant inroads in education, it is essential to understand what factors will influence this technology's adoption and acceptance. In this work, we explore factors influencing the adoption of VR for hands-on practical learning around the world based on the Unified Theory of Acceptance and Use of Technology and three additional constructs. We also performed a cross-cultural analysis to examine the model fit for developed and developing countries and regions. Moreover, through open-ended questions, we gauge the overall feeling people in these countries have regarding VR for practical learning and how it compares with regular online learning.

10.
Front Pharmacol ; 13: 986436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408261

RESUMO

It is widely acknowledged that the climacteric syndrome negatively affects women's quality of life and leads to cerebral ischemic injury, osteoporosis and cardiovascular disease. One of the main active ingredients in Radix Scutellariae, Baicalin, has been established to possess a wide range of pharmacological effects and is beneficial in enhancing osteogenic differentiation and cardiovascular disease. Baicalin's profound metabolic impact on various stem cell populations and their fate specification could improve the efficiency of stem cell therapy for climacteric syndrome. However, Baicalin-mediated processes are complex and many of the underlying mechanisms are not fully fathomed yet. This review aims to shed light on the regulatory role of Baicalin on the diverse behaviors of distinct stem cell populations and provide a good cell source for stem cell therapy to broaden the therapeutic landscape for climacteric syndrome patients.

11.
Mol Nutr Food Res ; : e2200337, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36408889

RESUMO

SCOPE: Gastrointestinal side effects are frequently observed in patients receiving medical radiation therapy. As Lacticaseibacillus casei ATCC334 potentially affects microbial ecosystem, the study hypothesizes that it may improve radiation-induced intestinal injury in rats by modulating the "gut microbiota-metabolite-barrier axis." METHODS AND RESULTS: Rats are fed one of three or no doses of L. casei ATCC334 for 7 days and then expose to a single dose of 9 Gy X-ray total abdominal irradiation. Supplementation with L. casei ATCC334 promote the proliferation of intestinal stem cells (ISCs), increase the expression of tight junction proteins, reduce intestinal permeability, and protect intestinal barrier integrity. Moreover, 16S rRNA sequencing show that medium and high doses of L. casei ATCC334 inhibit the growth of Escherichia/Shigella and favor Akkermansia proliferation. L. casei ATCC334 intervention reprogram the metabolic profile and inhibit putrescine production but promote alpha-linolenic acid (ALA) production. Notably, a decrease in putrescine and an increase in ALA are significantly correlated with the proliferation of ISCs and enhanced intestinal barrier function following L. casei ATCC334 intervention. CONCLUSION: These results highlight that medium and high doses of L. casei ATCC334 alleviate radiation-induced intestinal damage by enhancing the mucosal barrier and remodeling the gut microbiota structure and metabolic activity.

12.
Plant J ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380696

RESUMO

'Candidatus Phytoplasma tritici' ('Ca. P. tritici') is an insect-borne obligate pathogen that infects wheat (Triticum aestivum) causing wheat blue dwarf disease, and leads to yield losses. SWP12 is a potential effector secreted by 'Ca. P. tritici' that manipulates host processes to create an environment conducive to phytoplasma colonization, but the detailed mechanism of action remains to be investigated. In this study, the expression of SWP12 weakened the basal immunity of Nicotiana benthamiana and promoted leaf colonization by Phytophthora parasitica, Sclerotinia sclerotiorum, and tobacco mild green mosaic virus. Moreover, the expression of SWP12 in wheat plants promoted phytoplasma colonization. Triticum aestivum WRKY74 and N. benthamiana WRKY17 were identified as host targets of SWP12. The expression of TaWRKY74 triggered reactive oxygen species bursts, upregulated defense-related genes, and decreased TaCRR6 transcription, leading to reductions in NADH dehydrogenase complex (NDH) activity. Expression of TaWRKY74 in wheat increased plant resistance to 'Ca. P. tritici', and silencing of TaWRKY74 enhanced plant susceptibility, which indicates that TaWRKY74 is a positive regulator of wheat resistance to 'Ca. P. tritici'. We showed that SWP12 weakens plant resistance and promotes 'Ca. P. tritici' colonization by destabilizing TaWRKY74.

13.
J Am Chem Soc ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36417425

RESUMO

Phosphine ligands are the most important class of ligands for cross-coupling reactions due to their unique electronic and steric properties. However, metalloproteins generally rely on nitrogen, sulfur, or oxygen ligands. Here, we report the genetic incorporation of P3BF, which contains a biocompatible borane-protected phosphine, into proteins. This step is followed by a straightforward one-pot strategy to perform deboronation and palladium coordination in aqueous and aerobic conditions. The genetically encoded phosphine ligand P3BF should significantly expand our ability to design functional metalloproteins.

14.
Cancer Cell Int ; 22(1): 347, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371186

RESUMO

BACKGROUND: Genes related to the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex are frequently mutated across cancers. SWI/SNF-mutant tumors are vulnerable to synthetic lethal inhibitors. However, the landscape of SWI/SNF mutations and their associations with tumor mutational burden (TMB), microsatellite instability (MSI) status, and response to immune checkpoint inhibitors (ICIs) have not been elucidated in large real-world Chinese patient cohorts. METHODS: The mutational rates and variation types of six SWI/SNF complex genes (ARID1A, ARID1B, ARID2, SMARCA4, SMARCB1, and PBRM1) were analyzed retrospectively by integrating next-generation sequencing data of 4591 cases covering 18 cancer types. Thereafter, characteristics of SWI/SNF mutations were depicted and the TMB and MSI status and therapeutic effects of ICIs in the SWI/SNF-mutant and SWI/SNF-non-mutant groups were compared. RESULTS: SWI/SNF mutations were observed in 21.8% of tumors. Endometrial (54.1%), gallbladder and biliary tract (43.4%), and gastric (33.9%) cancers exhibited remarkably higher SWI/SNF mutational rates than other malignancies. Further, ARID1A was the most frequently mutated SWI/SNF gene, and ARID1A D1850fs was identified as relatively crucial. The TMB value, TMB-high (TMB-H), and MSI-high (MSI-H) proportions corresponding to SWI/SNF-mutant cancers were significantly higher than those corresponding to SWI/SNF-non-mutant cancers (25.8 vs. 5.6 mutations/Mb, 44.3% vs. 10.3%, and 16.0% vs. 0.9%, respectively; all p < 0.0001). Furthermore, these indices were even higher for tumors with co-mutations of SWI/SNF genes and MLL2/3. Regarding immunotherapeutic effects, patients with SWI/SNF variations showed significantly longer progression-free survival (PFS) rates than their SWI/SNF-non-mutant counterparts (hazard ratio [HR], 0.56 [95% confidence interval {CI} 0.44-0.72]; p < 0.0001), and PBRM1 mutations were associated with relatively better ICI treatment outcomes than the other SWI/SNF gene mutations (HR, 0.21 [95% CI 0.12-0.37]; p = 0.0007). Additionally, patients in the SWI/SNF-mutant + TMB-H (HR, 0.48 [95% CI 0.37-0.54]; p < 0.0001) cohorts had longer PFS rates than those in the SWI/SNF-non-mutant + TMB-low cohort. CONCLUSIONS: SWI/SNF complex genes are frequently mutated and are closely associated with TMB-H status, MSI-H status, and superior ICI treatment response in several cancers, such as colorectal cancer, gastric cancer, and non-small cell lung cancer. These findings emphasize the necessity and importance of molecular-level detection and interpretation of SWI/SNF complex mutations.

15.
Clin Exp Metastasis ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36380015

RESUMO

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.

16.
Technol Cancer Res Treat ; 21: 15330338221136716, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36344243

RESUMO

Radical treatment of malignant solid tumors should aim to be less traumatic, precise, and effective. OncoCiDia, as a noninvasive, sequential dual-targeting, small-molecule, broad spectrum anticancer theranostic approach, may fulfill these requirements of solid cancer (Onco) treatment with both tumoricidal (Ci) and diagnostic (Dia) effects. However, it is unlikely to cure patients with cancer, especially those with large and irregular tumors and with tumors residing in certain organs, such as the brain and pancreas, because of insufficient necrosis generation. To amplify ablative efficacy, this shortcoming could be overcome by combining high-intensity focused ultrasound (HIFU) with the use of a vascular-disrupting agent (VDA) and a radioactively labeled necrosis avid compound (NAC), such as 131I-Hypericin (131I-Hyp), which are the first and second targeting drugs used in OncoCiDia. This study proposes the combined use of OncoCiDia and HIFU (Onco-HIFU-CiDia) as a synergistic treatment for malignant tumors to achieve a curative multimodality and multidrug regimen for patients with solid cancers, in accordance with the current trend of cancer patient care.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Radioisótopos do Iodo , Necrose/terapia
17.
J Am Med Dir Assoc ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36351463

RESUMO

OBJECTIVES: To investigate excessive dietary salt intake as an independent risk factor of cognitive impairment and dementia in older adults. DESIGN: Prospective, population-based cohort study. SETTINGS AND PARTICIPANTS: Two thousand forty-one community residents aged ≥60 years were recruited between April 2007 and August 2009 from the Shandong area of China. MEASUREMENTS: Participants were classified into low, mild, moderate, and high salt intake groups according to urinary sodium measurements for 7 consecutive days. Global cognitive function was assessed at baseline and biennially thereafter using the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Dementia Rating Scale (DRS), and Informant Questionnaire on Cognitive Decline in the Elderly. Demographics and apolipoprotein E (APOE) genotype were also obtained for each participant. Participants were monitored for 11.4 ± 2.0 years. RESULTS: During follow-up, MMSE, MoCA, and DRS scores decreased progressively faster with increasing salt intake (Padjustment < 0.05 among all intake groups). In total, 319 participants (13.74 per 1000 person-years) developed cognitive impairment. Compared with the low salt intake group, cognitive impairment risk was increased by 75% in the mild group (Padjustment = 0.027), 180% in the moderate group (Padjustment < 0.001), and 330% in the high group (Padjustment < 0.001) after adjustment for age, education, mean, and variability in visit-to-visit systolic and diastolic blood pressure, and APOE genotype. The hazard ratio for cognitive impairment increased by 1.59 (95% CI 1.40-1.79) with each 1-SD increment in salt intake after confounder adjustment (Padjustment < 0.001). CONCLUSIONS AND IMPLICATIONS: Excessive dietary salt impairs cognitive function and increases cognitive impairment risk in older adults independently of known risk factors, including hypertension and APOE genotype.

18.
Acta Biomater ; 2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36384221

RESUMO

Transplantation of allogeneic adult spinal cord tissues (aSCTs) to replace the injured spinal cord, serves as a promising strategy in complete spinal cord injury (SCI) repair. However, in addition to allograft immune rejection, damage-associated molecular pattern (DAMP)-mediated inflammatory microenvironments greatly impair the survival and function of transplants. In this study, we aimed to regulate the immune microenvironment after aSCT implantation by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. The F-G/H hydrogel exhibited the capacities of DAMP scavenging, sustainably released anti-inflammatory cytokines, and reduced lymphocyte accumulation, thereby modulating the immune response and enhancing the survival and function of aSCTs. When the hydrogel was used in combination with a systemic immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. This biomaterial-based immunomodulatory strategy may provide the potential for spinal cord graft replacement for treating SCI. STATEMENT OF SIGNIFICANCE: In this study, we aimed to regulate the immune microenvironment by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. We found that with the treatment of F-G/H hydrogel, the aSCT survival and function was significantly improved, as a result of reducing recruitment and activation of immune cells through TLR- and ST-2- related signaling. With the combination of immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. Findings from this work suggest the potential application of the F-G/H as a biomaterial-based immunoregulatory strategy for improving the therapeutic efficiency of the transplanted spinal cord graft for spinal cord injury repair.

19.
J Am Chem Soc ; 144(45): 20815-20824, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36322830

RESUMO

RNA is challenging to target with bioactive small molecules, particularly those of low molecular weight that bind with sufficient affinity and specificity. In this report, we developed a platform to address this challenge, affording a novel bioactive interaction. An RNA-focused small-molecule fragment collection (n = 2500) was constructed by analyzing features in all publicly reported compounds that bind RNA, the largest collection of RNA-focused fragments to date. The RNA-binding landscape for each fragment was studied by using a library-versus-library selection with an RNA library displaying a discrete structural element, probing over 12.8 million interactions, the greatest number of interactions between fragments and biomolecules probed experimentally. Mining of this dataset across the human transcriptome defined a drug-like fragment that potently and specifically targeted the microRNA-372 hairpin precursor, inhibiting its processing into the mature, functional microRNA and alleviating invasive and proliferative oncogenic phenotypes in gastric cancer cells. Importantly, this fragment has favorable properties, including an affinity for the RNA target of 300 ± 130 nM, a molecular weight of 273 Da, and quantitative estimate of drug-likeness (QED) score of 0.8. (For comparison, the mean QED of oral medicines is 0.6 ± 0.2). Thus, these studies demonstrate that a low-molecular weight, fragment-like compound can specifically and potently modulate RNA targets.


Assuntos
MicroRNAs , Bibliotecas de Moléculas Pequenas , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Peso Molecular , MicroRNAs/metabolismo , Carcinogênese
20.
Dev Psychobiol ; 64(8): e22335, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36426785

RESUMO

Recent studies have found that adults have stronger attentional bias toward neutral infant faces than emotional (positive or negative) infant faces. This phenomenon may derive from uncertainty over neutral expressions. To test this hypothesis, we recruited 176 participants to examine the relationship between their attentional bias toward neutral infant faces (with neutral adult faces as a comparison baseline) and their level of certainty in their appraisal of emotional valence through eye-tracking indices. The results showed that participants had a longer dwell time and higher fixation counts for infant faces than for adult faces and that a more uncertain appraisal of facial expressions positively predicted attentional bias toward neutral infant faces. Therefore, this study preliminarily demonstrates that emotional uncertainty heightens adults' attentional bias toward infant faces with neutral expressions.

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