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1.
J Cancer Res Clin Oncol ; 150(6): 317, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914670

RESUMEN

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.


Asunto(s)
Neoplasias de la Mama , Antígeno CD24 , Proliferación Celular , Progresión de la Enfermedad , MicroARNs , ARN Largo no Codificante , Humanos , Antígeno CD24/genética , Antígeno CD24/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , MicroARNs/genética , Animales , Ratones , ARN Largo no Codificante/genética , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Movimiento Celular/genética , Ratones Endogámicos BALB C , Pronóstico
2.
Maturitas ; 187: 108040, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38852490

RESUMEN

Acupoint-stimulating therapies have often been used to manage stroke-related spasticity and motor dysfunction. However, the effects of different acupoint-stimulating therapies in older stroke survivors have been unclear. This systematic review and network meta-analysis compared the effects of different acupoint-stimulating therapies in managing spasticity and motor dysfunction in older stroke survivors. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched 7 databases for studies published up to July 2023. Inclusion criteria were: (1) older adults with strokes; (2) treatments were acupoint-stimulating therapies; (3) a control group did not receive acupoint-stimulating therapy, or the study compared different acupoint-stimulating therapies; and (4) outcomes included spasticity and motor function. Methodological quality was assessed with Risk-of-bias tool for randomized trials version 2, while R and Metainsight were used to conduct the network meta-analysis. We analyzed 27 studies and the results showed that non-invasive electroacupuncture and warm acupuncture were more effective in reducing spasticity than conventional acupuncture (standardized mean difference and 95 % confidence intervals = 1.35/1.19 [0.57; 2.13/0.54; 1.83]) and invasive electroacupuncture (standardized mean difference and 95 % confidence intervals = 0.96/0.80 [0.12; 1.80/0.08; 1.51]). Conventional acupuncture and invasive electroacupuncture were effective in improving motor function (standardized mean difference and 95 % confidence intervals = 0.99/1.41 [0.42; 1.56/0.54; 2.28]). However, there was significant inconsistency for the effects of invasive electroacupuncture between studies. Our findings suggest that for older stroke survivors with spasticity, non-invasive electroacupuncture and warm acupuncture are appropriate, whereas conventional acupuncture is more appropriate for patients aiming for motor recovery. SYSTEMATIC REVIEW REGISTRATION: This study was registered in the PROSPERO database (CRD42023442202).

3.
Water Res ; 258: 121788, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38810599

RESUMEN

While waters might be contaminated by oocysts from >40 Cryptosporidium species, only viable oocysts of C. parvum and C. hominis truly pose the main health risk to the immunocompetent population. Oocyst viability is also an important but often neglected risk factor in monitoring waterborne parasites. However, commonly used methods in water monitoring and surveys cannot distinguish species (microscopic observation) or oocyst viability (PCR), as dead oocysts in water could retain gross structure and DNA content for weeks to months. Here, we report new TaqMan qRT-PCR/qPCR assays for quantitative detection of viable C. parvum and C. hominis oocysts. By targeting a hypothetical protein-encoding gene cgd6_3920 that is highly expressed in oocysts and variable between species, the qRT-PCR/qPCR assays achieve excellent analytical specificity and sensitivity (limit of quantification [LOQ] = 0.25 and 1.0 oocyst/reaction). Using calibration curves, the number and ratio of viable oocysts in specimens could be calculated. Additionally, we also establish a TaqMan-18S qPCR for cost-effective screening of pan-Cryptosporidium-positive specimens (LOQ = 0.1 oocyst/reaction). The assay feasibility is validated using field water (N = 43) and soil (79) specimens from 17 locations in Changchun, China, which detects four Cryptosporidium species from seven locations, including three gp60-subtypes (i.e., IIdA19G1, IIdA17G1 and IIdA24G2) of C. parvum oocysts showing varied viability ratios. These new TaqMan q(RT)-PCR assays supplement current methods in the survey of waters and other samples (e.g., surfaces, foods and beverages), and are applicable to assessing the efficiency of oocyst deactivation protocols.


Asunto(s)
Cryptosporidium parvum , Cryptosporidium , Oocistos , Cryptosporidium/genética , Factores de Riesgo , Salud Pública , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos
4.
Pestic Biochem Physiol ; 200: 105839, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38582601

RESUMEN

Lepidopteran insects are refractory to RNA interference (RNAi) response, especially to orally delivered double-stranded RNA (dsRNA). High nuclease activity in the midgut lumen is proposed as one of the major reasons for RNAi insensitivity. We identified three dsRNase genes highly expressed in the midgut of fall armyworm (FAW), Spodoptera frugiperda. The genomic region harboring those three dsRNase genes was deleted using the CRISPR-Cas9-mediated genome editing method. A homozygous line with deletion of three dsRNase genes was produced. dsRNA degradation by midgut lumen contents of mutant larvae was lower than in wild-type larvae. Feeding dsRNA targeting the inhibitor of apoptosis (IAP) gene increased knockdown of the target gene and mortality in mutants compared to wild-type larvae. These results suggest that dsRNases in the midgut contribute to RNAi inefficiency in FAW. Formulations that protect dsRNA from dsRNase degradation may improve RNAi efficiency in FAW and other lepidopteran insects.


Asunto(s)
Sistemas CRISPR-Cas , ARN Bicatenario , Animales , Interferencia de ARN , Spodoptera/genética , Spodoptera/metabolismo , ARN Bicatenario/genética , ARN Bicatenario/metabolismo , Insectos/genética , Larva/genética , Larva/metabolismo
5.
Trends Parasitol ; 40(4): 280-282, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38485578

RESUMEN

Xu and colleagues recently revealed the critical role of Cryptosporidium's feeder organelle in nutrient uptake, showcasing the parasite's ability to harness glucose and glucose-6-phosphate from host cells. This illuminates the sophisticated energy metabolism and survival strategies of the parasite, highlighting potential therapeutic targets.


Asunto(s)
Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Humanos , Criptosporidiosis/parasitología , Orgánulos/metabolismo , Metabolismo Energético
6.
mBio ; 15(2): e0315823, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38265238

RESUMEN

The zoonotic Cryptosporidium parvum is a global contributor to infantile diarrheal diseases and opportunistic infections in immunocompromised or weakened individuals. Like other apicomplexans, it possesses several specialized secretory organelles, including micronemes, rhoptry, and dense granules. However, the understanding of cryptosporidial micronemal composition and secretory pathway remains limited. Here, we report a new micronemal protein in C. parvum, namely, thrombospondin (TSP)-repeat domain-containing protein-4 (CpTSP4), providing insights into these ambiguities. Immunostaining and enzyme-linked assays show that CpTSP4 is prestored in the micronemes of unexcysted sporozoites but secreted during sporozoite excystation, gliding, and invasion. In excysted sporozoites, CpTSP4 is also distributed on the two central microtubules unique to Cryptosporidium. The secretion and microtubular distribution could be completely blocked by the selective kinesin-5 inhibitors SB-743921 and SB-715992, resulting in the accumulation of CpTSP4 in micronemes. These support the kinesin-dependent microtubular trafficking of CpTSP4 for secretion. We also localize γ-tubulin, consistent with kinesin-dependent anterograde trafficking. Additionally, recombinant CpTSP4 displays nanomolar binding affinity to the host cell surface, for which heparin acts as one of the host ligands. A novel heparin-binding motif is identified and validated biochemically for its contribution to the adhesive property of CpTSP4 by peptide competition assays and site-directed mutagenesis. These findings shed light on the mechanisms of intracellular trafficking and secretion of a cryptosporidial micronemal protein and the interaction of a TSP-family protein with host cells.IMPORTANCECryptosporidium parvum is a globally distributed apicomplexan parasite infecting humans and/or animals. Like other apicomplexans, it possesses specialized secretory organelles in the zoites, in which micronemes discharge molecules to facilitate the movement and invasion of zoites. Although past and recent studies have identified several proteins in cryptosporidial micronemes, our understanding of the composition, secretory pathways, and domain-ligand interactions of micronemal proteins remains limited. This study identifies a new micronemal protein, namely, CpTSP4, that is discharged during excystation, gliding, and invasion of C. parvum sporozoites. The CpTSP4 secretion depends on the intracellular trafficking on the two Cryptosporidium-unique microtubes that could be blocked by kinesin-5/Eg5 inhibitors. Additionally, a novel heparin-binding motif is identified and biochemically validated, which contributes to the nanomolar binding affinity of CpTSP4 to host cells. These findings indicate that kinesin-dependent microtubular trafficking is critical to CpTSP4 secretion, and heparin/heparan sulfate is one of the ligands for this micronemal protein.


Asunto(s)
Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Humanos , Animales , Cryptosporidium parvum/metabolismo , Criptosporidiosis/metabolismo , Cinesinas/metabolismo , Microtúbulos/metabolismo , Esporozoítos/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Heparina/metabolismo
7.
Geriatr Nurs ; 55: 183-190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38007907

RESUMEN

INTRODUCTION: Mind-body exercises (MBEs) were shown to be effective in managing chronic pain among older adults in several recent studies. However, the differences in the effects of different MBEs remained unclear. OBJECTIVE: To compare the effects of different MBEs in managing chronic pain in older adults. METHODS: Eight databases were searched for studies published between 2012 and 2023, and 14 studies were included in this systematic review and network meta-analysis (NMA). The NMA was performed using R and Metainsight. RESULTS: Results showed that tai chi and yoga were effective in alleviating chronic pain, but their effects were not superior to traditional physical exercises and other MBEs. In addition, none of the MBEs were shown to be effective in mitigating chronic pain-related disabilities. CONCLUSION: Tai chi and yoga can be used for relieving chronic pain in older adults; however, MBE programs alone were not sufficient to mitigate chronic pain-related disabilities.


Asunto(s)
Dolor Crónico , Taichi Chuan , Yoga , Humanos , Anciano , Dolor Crónico/terapia , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Ejercicio Físico
8.
Am J Orthod Dentofacial Orthop ; 165(3): 272-284.e3, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38108674

RESUMEN

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.


Asunto(s)
Aparatos Ortodóncicos Removibles , Técnicas de Movimiento Dental , Humanos , Análisis de Elementos Finitos , Incisivo , Aparatos Ortodóncicos , Fenómenos Biomecánicos
9.
J Agric Food Chem ; 71(42): 15497-15505, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37843053

RESUMEN

Azadirachtin has been used to control agricultural pests for a long time; however, the molecular mechanism of azadirachtin on lepidopterans is still not clear. In this study, the fourth instar larvae of fall armyworm were fed with azadirachtin, and then the ecdysis was blocked in the fourth instar larval stage (L4). The prothoracic glands (PGs) of the treated larvae were dissected for RNA sequencing to determine the effect of azadirachtin on ecdysis inhibition. Interestingly, one of the PG-enriched genes, the nuclear hormone receptor 3 (HR3), was decreased after azadirachtin treatment, which plays a critical role in the 20-hydroxyecdysone action during ecdysis. To deepen the understanding of azadirachtin on ecdysis, the HR3 was knocked out by using the CRISPR/Cas9 system, while the HR3 mutants displayed embryonic lethal phenotype; thus, the stage-specific function of HR3 during larval molting was not enabled to unfold. Hence, the siRNA was injected into the 24 h L4 larvae to knock down HR3. After 96 h, the injected larvae were blocked in the old cuticle during ecdysis which is consistent with the azadirachtin-treated larvae. Taken together, we envisioned that the inhibition of ecdysis in the fall armyworm after the azadirachtin treatment is due to an interference with the expression of HR3 in PG, resulting in larval mortality. The results in this study specified the understanding of azadirachtin on insect ecdysis and the function of HR3 in lepidopteran in vivo.


Asunto(s)
Muda , Receptores Citoplasmáticos y Nucleares , Animales , Muda/genética , Larva/metabolismo , Spodoptera/genética , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo
10.
Neurosci Lett ; 812: 137406, 2023 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-37480979

RESUMEN

BACKGROUND: This study aimed to assess the effectiveness of swimming exercise in alleviating mechanical hypersensitivity and peripheral nerve degeneration associated with a pre-clinical model of painful diabetic neuropathy (PDN). METHODS: This study is a pre-clinical study conducted using the streptozocin (STZ)-induced PDN rat model. Rats were randomly allocated to three groups: a vehicle group of non-diabetic rats (Vehicle, n = 9), a group of rats with PDN (PDN, n = 8), and a group of rats with PDN that performed a swimming exercise program (PDN-SW, n = 10). The swimming exercise program included daily 30-minute swimming exercise, 5 days per week for 4 weeks. Von Frey testing was used to monitor hindpaw mechanical sensitivity over 4 weeks. Assessment of cutaneous peripheral nerve fiber integrity was performed after the 4-week study period via immunohistochemistry for protein gene product 9.5-positive (PGP9.5+) intra-epidermal nerve fiber density (IENFD) in hind-paw skin biopsies by a blinded investigator. RESULTS: The results showed that swimming exercise mitigated but did not fully reverse mechanical hypersensitivity in rats with PDN. Immunohistochemical testing revealed that the rats in the PDN-SW group retained higher PGP9.5+ IENFD compared to the PDN group but did not reach normal levels of the Vehicle group. CONCLUSIONS: The results of this study indicate that swimming exercise can mitigate mechanical hypersensitivity and degeneration of peripheral nerve fibers in rats with experimental PDN.


Asunto(s)
Diabetes Mellitus Experimental , Neuropatías Diabéticas , Ratas , Animales , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Natación , Fibras Nerviosas/metabolismo , Nervios Periféricos/metabolismo
11.
J Infect Dis ; 228(10): 1430-1440, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37418629

RESUMEN

BACKGROUND: Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo. METHODS: Cryptosporidium tyzzeri, a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis, was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model. RESULTS: Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri. CONCLUSIONS: Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.


Asunto(s)
Antiprotozoarios , Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Animales , Ratones , Humanos , Paromomicina/farmacología , Paromomicina/uso terapéutico , Criptosporidiosis/parasitología , Vorinostat/farmacología , Vorinostat/uso terapéutico , Antiprotozoarios/farmacología , Docetaxel/farmacología , Docetaxel/uso terapéutico , Análisis Costo-Beneficio , Fitomejoramiento
12.
Artículo en Inglés | MEDLINE | ID: mdl-37467937

RESUMEN

OBJECTIVE: To assess and compare the effects of different stretching exercise programs on pain, stiffness, and physical function disability in older adults with knee osteoarthritis (KOA). DATA SOURCES: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for network meta-analysis (NMA). Relevant randomized controlled trials were identified by searching 7 databases up to December 2022. STUDY SELECTION: Inclusion criteria included (1) older adults with KOA; (2) intervention included stretching exercises; (3) control groups received no stretching exercise; and (4) outcome measurements included pain, stiffness, or physical function disability. Methodological quality was assessed using the Cochrane risk-of-bias tool for randomized trials version 2. DATA EXTRACTION: NMA was performed using R and MetaInsight, with results presented as a standardized mean difference (SMD) with 95% confidence interval (CI). DATA SYNTHESIS: We examined 17 studies, and NMA results indicated that proprioceptive neuromuscular facilitation (PNF) stretching, mind-body exercises, and multi-component exercise programs were effective in mitigating pain in older adults with KOA (SMD=2.54 [95% CI: 1.23; 3.84], SMD=1.09 [95% CI: 0.27; 1.92], SMD=0.57 [95% CI: 0.06; 1.09]). Moreover, mind-body exercises and multi-component exercises were the most effective programs in reducing stiffness (SMD=1.31 [95% CI: 0.12; 2.51]) and physical function disability (SMD=1.67 [95% CI: 0.01; 3.33]) in older adults with KOA, respectively. CONCLUSION: Findings suggest that PNF stretching, mind-body exercises, and multi-component exercises can be incorporated into exercise programs to better mitigate pain, stiffness, and physical function disability in older adults with KOA.

13.
Front Neurol ; 14: 1124059, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37305754

RESUMEN

Purpose: In this study, we described "PT for Sleep Apnea", a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea (OSA). Methods: The application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City (UMP), Vietnam, and National Cheng Kung University (NCKU), Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training. Results: The application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea. Conclusion: In the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with OSA.

14.
ACS Appl Mater Interfaces ; 15(19): 23922-23930, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37145874

RESUMEN

The unique ion-transport properties in nanoconfined pores enable nanofluidic devices with great potential in harvesting osmotic energy. The energy conversion performance could be significantly improved by the precise regulation of the "permeability-selectivity" trade-off and the ion concentration polarization effect. Here, we take the advantage of electrodeposition technique to fabricate a Janus metal-organic framework (J-MOF) membrane that possesses rapid ion-transport capability and impeccable ion selectivity. The asymmetric structure and asymmetric surface charge distribution of the J-MOF device can suppress the ion concentration polarization effect and enhance the ion charge separation, exhibiting an improved energy harvesting performance. An output power density of 3.44 W/m2 has been achieved with the J-MOF membrane at a 1000-fold concentration gradient. This work provides a new strategy for fabricating high-performance energy-harvesting devices.

15.
Am J Orthod Dentofacial Orthop ; 163(6): 811-824.e2, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36964108

RESUMEN

INTRODUCTION: Compared with fixed treatments, clear aligners (CAs) have the advantages of comfort, esthetics, and hygiene, and are popular among patients and orthodontists. However, CAs exhibit control deficiencies in extraction patients because of insufficient root control and retention effects. These deficiencies can magnify biomechanical differences in bimaxillary dentition, further causing different orthodontic requirements between maxillary and mandibular dentition. This study aimed to elaborate on the biomechanical characteristics of bimaxillary dentition in extraction space closure and provided feasible biomechanical compensation strategies for use in clinical practice. METHODS: We constructed a 3-dimensional (3D) bimaxillary model based on patient data. Several 3D modeling-related software was used to generate a standard first premolar extraction model, CAs, and attachments. Subsequently, finite element analysis was performed to demonstrate the biomechanical effects. RESULTS: The maxillary and mandibular dentition showed a roller coaster effect during space closure. Compared with the maxillary dentition, the mandibular posterior teeth exhibited stronger relative anchorage causing greater anterior teeth retraction. The tipping and vertical movements of the anterior teeth were related to tooth length. The longer the anterior tooth, the less tipping and greater vertical displacement occurred. Generally, when having the same retraction distance, the mandibular dentition exhibited greater retroclination and fewer extrusions. Both mechanical and retention compensations should be considered to prevent these unwanted tipping movements. Adding specific attachments to bimaxillary dentitions compensated for the retention and root control deficiencies of CAs. CONCLUSIONS: When applying CAs to extraction patients, different biomechanical effects can present in the bimaxillary dentition because of specific dentition morphologies. To effectively treat these patients, mechanical compensation through overcorrection of the target position should be designed on the basis of bimaxillary control deficiencies, and retention compensation by adding specific attachments should also be considered according to the overcorrections.


Asunto(s)
Aparatos Ortodóncicos Removibles , Técnicas de Movimiento Dental , Humanos , Técnicas de Movimiento Dental/métodos , Análisis de Elementos Finitos , Estética Dental , Mandíbula , Fenómenos Biomecánicos
16.
PLoS Negl Trop Dis ; 17(3): e0011217, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36972284

RESUMEN

Cryptosporidium parvum is a globally distributed zoonotic protozoan parasite that causes moderate to severe, sometime deadly, watery diarrhea in humans and animals, for which fully effective treatments are yet unavailable. In studying the mechanism of action of drugs against intracellular pathogens, it is important to validate whether the observed anti-infective activity is attributed to the drug action on the pathogen or host target. For the epicellular parasite Cryptosporidium, we have previously developed a concept that the host cells with significantly increased drug tolerance by transient overexpression of the multidrug resistance protein-1 (MDR1) could be utilized to evaluate whether and how much the observed anti-cryptosporidial activity of an inhibitor was attributed to the inhibitor's action on the parasite target. However, the transient transfection model was only applicable to evaluating native MDR1 substrates. Here we report an advanced model using stable MDR1-transgenic HCT-8 cells that allows rapid development of novel resistance to non-MDR1 substrates by multiple rounds of drug selection. Using the new model, we successfully validated that nitazoxanide, a non-MDR1 substrate and the only FDA-approved drug to treat human cryptosporidiosis, killed C. parvum by fully (100%) acting on the parasite target. We also confirmed that paclitaxel acted fully on the parasite target, while several other inhibitors including mitoxantrone, doxorubicin, vincristine and ivermectin acted partially on the parasite targets. Additionally, we developed mathematical models to quantify the proportional contribution of the on-parasite-target effect to the observed anti-cryptosporidial activity and to evaluate the relationships between several in vitro parameters, including antiparasitic efficacy (ECi), cytotoxicity (TCi), selectivity index (SI) and Hill slope (h). Owning to the promiscuity of the MDR1 efflux pump, the MDR1-transgenic host cell model could be applied to assess the on-parasite-target effects of newly identified hits/leads, either substrates or non-substrates of MDR1, against Cryptosporidium or other epicellular pathogens.


Asunto(s)
Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Parásitos , Animales , Humanos , Cryptosporidium parvum/genética , Criptosporidiosis/parasitología , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/uso terapéutico , Algoritmos
17.
J Invest Surg ; 36(1): 2172488, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-36775654

RESUMEN

PURPOSE: Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer. METHODS: We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model. RESULTS: A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493-9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding. CONCLUSIONS: Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/cirugía , Puntaje de Propensión , Readmisión del Paciente , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Gastrectomía/efectos adversos , Lactato Deshidrogenasas
18.
Am J Orthod Dentofacial Orthop ; 163(5): 628-644.e11, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36801091

RESUMEN

INTRODUCTION: Clear aligners (CAs) have attracted increasing attention from patients and orthodontists because of their excellent esthetics and comfort. However, treating tooth extraction patients with CAs is difficult because their biomechanical effects are more complicated than those of traditional appliances. This study aimed to analyze the biomechanical effect of CAs in extraction space closure under different anchorage controls, including moderate, direct strong, and indirect strong anchorage. It could provide several new cognitions for anchorage control with CAs through finite element analysis, further directing clinical practice. METHODS: A 3-dimensional maxillary model was generated by combining cone-beam computed tomography and intraoral scan data. Three-dimensional modeling software was used to construct a standard first premolar extraction model, temporary anchorage devices, and CAs. Subsequently, finite element analysis was performed to simulate space closure under different anchorage controls. RESULTS: Direct strong anchorage was beneficial for reducing the clockwise occlusal plane rotation, whereas indirect anchorage was conducive for anterior teeth inclination control. In the direct strong anchorage group, an increase in the retraction force would require more specific anterior teeth overcorrection to resist the tipping movement, mainly including lingual root control of the central incisor, followed by distal root control of the canine, lingual root control of the lateral incisor, distal root control of the lateral incisor, and distal root control of the central incisor. However, the retraction force could not eliminate the mesial movement of the posterior teeth, possibly causing a reciprocating motion during treatment. In indirect strong groups, when the button was close to the center of the crown, the second premolar presented less mesial and buccal tipping but more intrusion. CONCLUSIONS: The 3 anchorage groups showed significantly different biomechanical effects in both the anterior and posterior teeth. Specific overcorrection or compensation forces should be considered when using different anchorage types. The moderate and indirect strong anchorages have a more stable and single-force system and could be reliable models in investigating the precise control of future tooth extraction patients.


Asunto(s)
Métodos de Anclaje en Ortodoncia , Aparatos Ortodóncicos Removibles , Análisis de Elementos Finitos , Estética Dental , Incisivo , Diente Premolar/cirugía , Maxilar , Técnicas de Movimiento Dental/métodos , Fenómenos Biomecánicos
19.
Investig Clin Urol ; 64(1): 20-30, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36629062

RESUMEN

PURPOSE: To evaluate the efficacy and safety of Quisqualis indica in men with moderate lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 135 subjects with International Prostate Symptom Score (IPSS) of 8-19 were randomized in 2 centers from June 2018 to April 2019. Patients were assigned into one of the three groups: a low-dose group (LG, 1,000 mg Q. indica), a high-dose group (HG, 2,000 mg Q. indica) or a placebo group (PG). The primary endpoint was the change of IPSS at the end of treatment from baseline. Secondary end points included the changes of prostate specific antigen, testosterone, dihydrotestosterone, maximum urinary flow rate (Qmax), postvoid residual volume (PVR) and International Index of Erectile Function-5 (IIEF-5), with drug safety. RESULTS: 113 patients were able to finish the study. Compared to the PG, total IPSS in the LG and the HG was significantly improved at 6 weeks and 12 weeks. For IPSS subscores, LG showed improvements in all except for urgency and quality of life at 6 weeks. HG showed improvements in incomplete emptying and frequency at 6 weeks and 12 weeks along with improvements in intermittency, straining, and quality of life at 12 weeks. For IIEF-5 subscores, orgasmic function and overall satisfaction improved in HG when compared to PG at 12 weeks. Lastly, increase of Qmax and decrease of PVR was observed at 6 weeks in LG. CONCLUSIONS: 12-week treatment with Q. indica has a therapeutic effect and is well tolerated in patients with LUTS.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/tratamiento farmacológico , Calidad de Vida , Resultado del Tratamiento
20.
World J Mens Health ; 41(3): 692-700, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36593713

RESUMEN

PURPOSE: To evaluated the efficacy and safety of gelatinized Maca (Lepidium meyenii) for eugonadal patients with late onset hypogonadism symptoms (LOH). MATERIALS AND METHODS: Participants were instructed to receive 1,000 mg of Maca or placebo, two pills at a time, three times per day for 12 weeks before food intake. To evaluate the efficacy of the drug, Aging Males' Symptoms scale (AMS), Androgen Deficiency in the Aging Males (ADAM), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) questionnaires, serologic tests (total testosterone and free testosterone, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride), body weight, and waist circumference were assessed at 4 and 12 weeks after treatment. RESULTS: A total of 80 participants were enrolled and randomly assigned to Maca treated group (n=41) or the placebo group (n=39). AMS, IIEF, and IPSS were significantly (p<0.05) improved in Maca treated group than in the placebo group. ADAM positive rate was also significantly (p<0.0001) decreased in Maca treated group. CONCLUSIONS: Maca may be considered an effective and safe treatment for eugonadal patients with late onset hypogonadism symptoms.

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