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1.
Biomed Pharmacother ; 175: 116700, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703505

RESUMEN

Late-onset hypogonadism (LOH) is an age-related disease in men characterized by decreased testosterone levels with symptoms such as decreased libido, erectile dysfunction, and depression. Thymus quinquecostatus Celakovski (TQC) is a plant used as a volatile oil in traditional medicine, and its bioactive compounds have anti-inflammatory potential. Based on this knowledge, the present study aimed to investigate the effects of TQC extract (TE) on LOH in TM3 Leydig cells and in an in vivo aging mouse model. The aqueous extract of T. quinquecostatus Celakovski (12.5, 25, and 50 µg/mL concentrations) was used to measure parameters such as cell viability, testosterone level, body weight, and gene expression, via in vivo studies. Interestingly, TE increased testosterone levels in TM3 cells in a dose-dependent manner without affecting cell viability. Furthermore, TE significantly increased the expression of genes involved in the cytochrome P450 family (Cyp11a1, Cyp17a1, Cyp19a1, and Srd5a2), which regulate testosterone biosynthesis. In aging mouse models, TE increased testosterone levels without affecting body weight and testicular tissue weight tissue of an aging animal group. In addition, the high-dose TE-treated group (50 mg/kg) showed significantly increased expression of the cytochrome p450 enzymes, similar to the in vitro results. Furthermore, HPLC-MS analysis confirmed the presence of caffeic acid and rosmarinic acid as bioactive compounds in TE. Thus, the results obtained in the present study confirmed that TQC and its bioactive compounds can be used for LOH treatment to enhance testosterone production.

2.
BMC Vet Res ; 20(1): 128, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561808

RESUMEN

BACKGROUND: Probiotics are beneficial for animal health and new potential probiotics need to be characterized for their prospective use in improving animal health. In this study, 32 bacterial strains were isolated from a Norwegian forest cat (castrated, 12 years old) and a Persian cat (castrated, 10 years old), which were privately owned and had indoor access. RESULTS: Lactobacillus rhamnosus CACC612 (CACC612) and Bifidobacterium animalis subsp. lactis CACC789 (CACC789) were selected as potential probiotics; characterization of the two strains showed equivalent acid tolerance, similar cell adhesion rates on the HT-29 monolayer cell line, and superior bile tolerance compared to Lactobacillus rhamnosus GG (LGG). Subsequently, they exhibited inhibitory effects against a broad spectrum of pathogenic bacteria, including E. coli (KCTC 2617), Salmonella Derby (NCCP 12,238), Salmonella Enteritidis (NCCP 14,546), Salmonella Typhimurium (NCCP 10,328), Clostridium difficile JCM 1296T. From evaluating host effects, the viability of the feline macrophage cell line (Fcwf-4) increased with the treatment of CACC612 or CACC789 (P < 0.05). The induced expression of immune-related genes such as IFN-γ, IL1ß, IL2, IL4, and TNF-α by immune stimulation was significantly attenuated by the treatment of CACC612 or CACC789 (P < 0.05). When 52 clinical factors of sera from 21 healthy cats were analyzed using partial least squares discriminant analysis (PLS-DA), the animals were obviously clustered before and after feeding with CACC612 or CACC789. In addition, hemoglobin and mean corpuscular hemoglobin concentration (MCHC) significantly increased after CACC612 feeding (P < 0.05). CONCLUSIONS: In this study, feline-originated probiotics were newly characterized and their potentially probiotic effects were evaluated. These results contribute to our understanding of the functional effects of feline-derived probiotics and support their industrial applications.


Asunto(s)
Bifidobacterium animalis , Lacticaseibacillus rhamnosus , Probióticos , Gatos , Animales , Escherichia coli , Probióticos/farmacología , Factor de Necrosis Tumoral alfa
3.
Artículo en Inglés | MEDLINE | ID: mdl-38650430

RESUMEN

Objective: Spinal intramedullary hemangioblastoma is a rare and highly vascularized benign tumor. The characteristics of the tumor, its corresponding location, and surgical outcomes remain unknown. The purpose of this study was to identify risk factors and strategies for neurologic deterioration following hemangioblastoma surgery. Methods: A comprehensive retrospective analysis was undertaken to evaluate patients who underwent surgical intervention for intramedullary hemangioblastoma at our institution from 1993 to 2022. Patients with at least one year of follow-up data were included. The analysis covered patient demographics, pre- and post-operative Modified McCormick Scale (MMCS), tumor location, and tumor size. Results: This study included 25 cases. One-year after surgery, neurological deterioration was observed in 5 (20.0%) cases, and neurological improvement was found in 9 (36.0%) cases. Five cases were ventrally located, and twelve cases were dorsally located. Ventrally located cases were larger in tumor axial size (p = 0.029) than dorsal location tumors, resulting in poorer follow-up MMCS and a higher prevalence of von Hippel-Lindau syndrome (VHL) (p = 0.042). Three of them were confirmed to be supplied by the anterior spinal artery. In the case of dorsally located cases, there was no neurologic deterioration. Conclusion: In intramedullary spinal cord hemangioblastomas, cases located ventrally had a higher incidence of neurological deterioration following surgery than those located dorsally or in intramedullary extramedullary cases. Ventrally located hemangioblastomas were larger than those in other locations. They were mainly supplied by the anterior spinal artery in VHL patients.

4.
Clin Spine Surg ; 37(4): 131-137, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38637933

RESUMEN

STUDY DESIGN: Single-center retrospective study. OBJECTIVE: The objective of this study is to identify the factors leading to repeat surgery in patients with cervical ossification of the longitudinal ligament (OPLL) during a minimal 8-year follow-up after the initial surgery. SUMMARY OF BACKGROUND DATA: The long-term effects of cervical OPLL are well known, but it's not always clear how many patients need to have surgery again because their neurological symptoms get worse. METHODS: This study is included 117 patients who underwent surgery for cervical OPLL and had a follow-up of at least 8 years. OPLL type, surgical extent, surgical method, and sagittal radiological parameters were measured, and OPLL characteristics were analyzed. RESULTS: The average age of patients at the time of surgery was 53.2 years, with a male-to-female ratio of 78:39. The median follow-up duration was 122 months (96-170 mo). Out of the total, 20 cases (17.1%) necessitated repeat surgery, among which 8 cases required surgery at the same site as the initial operation. The highest rate of repeat surgery was observed in patients who underwent total laminectomy without fusion (TL), where 6 out of 21 patients (29%) needed a second surgery, and 5 of these (23%) involved the same surgical site. Patients who underwent repeat surgery at the same site exhibited a greater range of motion (ROM) one year postsurgery (16.4 ± 8.5° vs. 23.1 ± 12.7°, P =0.041). In addition, the ROM at 1 year was higher in patients who underwent TL compared with those who had laminoplasty. Furthermore, the recurrence rate for hill-shape OPLL was higher at 30.8% compared to 10% for plateau-shape OPLL ( P = 0.05). CONCLUSION: Larger cervical ROM 1 year after surgery is related to repeat surgery at the same level as previous surgery, especially in laminectomy without fusion surgery.


Asunto(s)
Vértebras Cervicales , Osificación del Ligamento Longitudinal Posterior , Reoperación , Humanos , Osificación del Ligamento Longitudinal Posterior/cirugía , Osificación del Ligamento Longitudinal Posterior/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Estudios de Seguimiento , Anciano , Laminectomía , Adulto , Estudios Retrospectivos , Resultado del Tratamiento
5.
PLoS One ; 19(3): e0299792, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38536854

RESUMEN

Two probiotic candidates, Lactobacillus reuteri C1 (C1) and Lactobacillus acidophilus C5 (C5), which were previously isolated from canines, were evaluated in the present study. L. reuteri and L. acidophilus have anti-oxidant, anti-inflammatory, immune-enhancing, and anti-cancer properties and exhibit various probiotic effects in humans and animals. The strains C1 and C5 demonstrated good tolerance to acid and bile salt exposure, exhibited effective adhesion to HT-29 cell monolayer, and displayed sensitivity to antibiotics, thus affirming their probiotic characteristics. Moreover, C1 and C5 exhibited the ability to downregulate the expression of inducible NO synthase (iNOS), an immunomodulatory factor, leading to a reduction in NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. These strains also demonstrated potent anti-inflammatory effects in LPS-stimulated RAW 264.7 cells, achieved through the augmentation of anti-inflammatory cytokine IL-10 expression and the inhibition of pro-inflammatory cytokine IL-1ß expression. These anti-inflammatory effects of C1 and C5 were closely associated with the mitogen-activated protein kinase (MAPK) signaling pathway. The results of the present study suggest that the C1 and C5 probiotic candidates attenuate LPS-induced inflammation via the MAPK signaling pathway and the strains can be used as probiotics considering their anti-inflammatory potential.


Asunto(s)
Limosilactobacillus reuteri , Probióticos , Humanos , Animales , Perros , Lactobacillus , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Antiinflamatorios/farmacología , Sistema de Señalización de MAP Quinasas , Citocinas/metabolismo , Heces , Lactobacillus acidophilus/fisiología , Probióticos/farmacología , FN-kappa B/metabolismo
6.
Microorganisms ; 11(12)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38138034

RESUMEN

During weaning, piglets experience various stressor events that disrupt their gut microbiota and immune balance, decrease growth parameters, and increase mortality rates. In this study, we assessed the efficacy of Pediococcus pentosaceus CACC616 as a probiotic supplement. We characterized this strain and evaluated its effect on improving growth performance, modulating gut microbiota composition, and reducing noxious odor components in weaned piglets compared to a non-supplementary diet (control). During the 26-day period, 40 crossbred weaned piglets were randomly assigned to pens with 20 animals each in two groups: control and treatment groups with CACC616. On day 26, the treatment group exhibited a lower feed conversion ratio (FCR) and a significant alteration in gut microbial composition, correlating with improved growth parameters and gut health (p < 0.05). The treatment group also exhibited significantly reduced digestibility- and intestinal-environment-related noxious odor components (p < 0.05). The CACC616 strain effectively reduced pathogenic genera numbers, including Campylobacter, Mogibacterium, Escherichia-Shigella, and Desulfovibrio spp., with the treatment group exhibiting lower fecal calprotectin levels than the control group (p < 0.05). Overall, this study revealed that the functional probiotic CACC616 contributes to enhanced FCR and effectively modulates weaned piglets' inflammation and intestinal microbiota.

7.
Exp Mol Med ; 55(11): 2357-2375, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37907739

RESUMEN

Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III.


Asunto(s)
Dopamina , Proteínas de Transporte Vesicular de Monoaminas , Animales , Ratones , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Terminales Presinápticos/metabolismo , Sinapsinas/genética , Sinapsinas/metabolismo , Proteínas de Transporte Vesicular de Monoaminas/genética , Proteínas de Transporte Vesicular de Monoaminas/metabolismo
8.
J Anim Sci Technol ; 65(5): 1105-1109, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37969339

RESUMEN

Pedi coccus acidilactici CACC 537 was isolated from canine feces and reported to have probiotic properties. We aimed to characterize the potential probiotic properties of this strain by functional genomic analysis. Complete genome sequencing of P. acidilactici CACC 537 was performed using a PacBio RSII and Illumina platform, and contained one circular chromosome (2.0 Mb) with a 42% G + C content. The sequences were annotation revealed 1,897 protein-coding sequences, 15 rRNAs, and 56 tRNAs. It was determined that P. acidilactici CACC 537 genome carries genes known to be involved in the immune system, defense mechanisms, restriction-modification (R-M), and the CRISPR system. CACC 537 was shown to be beneficial in preventing pathogen infection during the fermentation process, help host immunity, and maintain intestinal health. These results provide for a comprehensive understanding of P. acidilactici and the development of industrial probiotic feed additives that can help improve host immunity and intestinal health.

10.
Nat Metab ; 5(9): 1506-1525, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37653043

RESUMEN

The lateral hypothalamic area (LHA) regulates food intake and energy balance. Although LHA neurons innervate adipose tissues, the identity of neurons that regulate fat is undefined. Here we show that GABRA5-positive neurons in LHA (GABRA5LHA) polysynaptically project to brown and white adipose tissues in the periphery. GABRA5LHA are a distinct subpopulation of GABAergic neurons and show decreased pacemaker firing in diet-induced obesity mouse models in males. Chemogenetic inhibition of GABRA5LHA suppresses fat thermogenesis and increases weight gain, whereas gene silencing of GABRA5 in LHA decreases weight gain. In the diet-induced obesity mouse model, GABRA5LHA are tonically inhibited by nearby reactive astrocytes releasing GABA, which is synthesized by monoamine oxidase B (Maob). Gene silencing of astrocytic Maob in LHA facilitates fat thermogenesis and reduces weight gain significantly without affecting food intake, which is recapitulated by administration of a Maob inhibitor, KDS2010. We propose that firing of GABRA5LHA suppresses fat accumulation and selective inhibition of astrocytic GABA is a molecular target for treating obesity.


Asunto(s)
Astrocitos , Obesidad , Masculino , Animales , Ratones , Aumento de Peso , Neuronas , Modelos Animales de Enfermedad , Monoaminooxidasa , Ácido gamma-Aminobutírico
11.
Exp Mol Med ; 55(8): 1720-1733, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37524868

RESUMEN

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/genética , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Hígado/metabolismo , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Factores de Transcripción/metabolismo , Humanos , Células Hep G2
12.
Biomed Pharmacother ; 163: 114802, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37146421

RESUMEN

Cancer-associated cachexia (CAC) is a multifactorial disorder characterized by an unrestricted loss of body weight as a result of muscle and adipose tissue atrophy. Cachexia is influenced by several factors, including decreased metabolic activity and food intake, an imbalance between energy uptake and expenditure, excessive catabolism, and inflammation. Cachexia is highly associated with all types of cancers responsible for more than half of cancer-related mortalities worldwide. In healthy individuals, adipose tissue significantly regulates energy balance and glucose homeostasis. However, in metastatic cancer patients, CAC occurs mainly because of an imbalance between muscle protein synthesis and degradation which are organized by certain extracellular ligands and associated signaling pathways. Under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1α) accumulated and translocated to the nucleus and activate numerous genes involved in cell survival, invasion, angiogenesis, metastasis, metabolic reprogramming, and cancer stemness. On the other hand, the ubiquitination proteasome pathway is inhibited during low O2 levels which promote muscle wasting in cancer patients. Therefore, understanding the mechanism of the HIF-1 pathway and its metabolic adaptation to biomolecules is important for developing a novel therapeutic method for cancer and cachexia therapy. Even though many HIF inhibitors are already in a clinical trial, their mechanism of action remains unknown. With this background, this review summarizes the basic concepts of cachexia, the role of inflammatory cytokines, pathways connected with cachexia with special reference to the HIF-1 pathway and its regulation, metabolic changes, and inhibitors of HIFs.


Asunto(s)
Caquexia , Neoplasias , Humanos , Caquexia/patología , Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias/complicaciones , Neoplasias/metabolismo , Tejido Adiposo/metabolismo , Hipoxia/metabolismo
13.
J Anim Sci Technol ; 65(2): 473-477, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37093924

RESUMEN

Lactobacillus amylovorus CACC736 was originated from swine feces in Korea. The complete genome sequences of the strain contained one circular chromosome (2,057,809 base pair [bp]) with 38.2% guanine-cytosine (GC) content and two circular plasmids, namely, pCACC736-1 and pCACC736-2. The predicted protein-coding genes, which are encoding the clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins, biosynthesis of bacteriocin (helveticin J), and the related proteins of the bile, acid tolerance. Notably, the genes related to vitamin B-group biosynthesis (riboflavin and cobalamin) were also found in L. amylovorus CACC736. Collectively, the complete genome sequence of the L. amylovorus CACC736 will aid in the development of functional probiotics in the animal industry.

14.
Metabolites ; 13(2)2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36837796

RESUMEN

Autism is a neurodevelopmental disorder for which the cause and treatment have yet not been determined. The polyunsaturated fatty acid (PUFA) levels change rapidly in the blood or cerebrospinal fluid of autistic children and PUFAs are closely related to autism spectrum disorder (ASD). This finding suggests that changes in lipid metabolism are associated with ASD and result in an altered distribution of phospholipids in cell membranes. To further understand ASD, it is necessary to analyze phospholipids in organs consisting of nerve cells, such as the brain. In this study, we investigated the phospholipid distribution in the brain tissue of valproic acid-induced autistic mice using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Phospholipids including phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were identified in each brain region and exhibited differences between the ASD and control groups. These phospholipids contain docosahexaenoic acid and arachidonic acid, which are important PUFAs for cell signaling and brain growth. We expect that the differences in phospholipids identified in the brain tissue of the ASD model with MALDI-MSI, in conjunction with conventional biological fluid analysis, will help to better understand changes in lipid metabolism in ASD.

15.
Dev Cell ; 58(4): 320-334.e8, 2023 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-36800996

RESUMEN

Exosomes transport a variety of macromolecules and modulate intercellular communication in physiology and disease. However, the regulation mechanisms that determine exosome contents during exosome biogenesis remain poorly understood. Here, we find that GPR143, an atypical GPCR, controls the endosomal sorting complex required for the transport (ESCRT)-dependent exosome biogenesis pathway. GPR143 interacts with HRS (an ESCRT-0 Subunit) and promotes its association to cargo proteins, such as EGFR, which subsequently enables selective protein sorting into intraluminal vesicles (ILVs) in multivesicular bodies (MVBs). GPR143 is elevated in multiple cancers, and quantitative proteomic and RNA profiling of exosomes in human cancer cell lines showed that the GPR143-ESCRT pathway promotes secretion of exosomes that carry unique cargo, including integrins signaling proteins. Through gain- and loss-of-function studies in mice, we show that GPR143 promotes metastasis by secreting exosomes and increasing cancer cell motility/invasion through the integrin/FAK/Src pathway. These findings provide a mechanism for regulating the exosomal proteome and demonstrate its ability to promote cancer cell motility.


Asunto(s)
Exosomas , Neoplasias , Humanos , Animales , Ratones , Exosomas/metabolismo , Proteómica , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Transporte de Proteínas , Transporte Biológico , Cuerpos Multivesiculares/metabolismo , Neoplasias/metabolismo , Proteínas del Ojo/metabolismo , Glicoproteínas de Membrana/metabolismo
16.
J Korean Neurosurg Soc ; 66(1): 44-52, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36050868

RESUMEN

OBJECTIVE: This study aimed to investigate the efficacy of transverse process (TP) hook system at the upper instrumented vertebra (UIV) for preventing screw pullout in adult spinal deformity surgery using the pedicle Hounsfield unit (HU) stratification based on K-means clustering. METHODS: We retrospectively reviewed 74 patients who underwent deformity correction surgery between 2011 and 2020 and were followed up for >12 months. Pre- and post-operative data were used to determine the incidence of screw pullout, UIV TP hook implementation, vertebral body HU, pedicle HU, and patient outcomes. Data was then statistically analyzed for assessment of efficacy and risk prediction using stratified HU at UIV level alongside the effect of the TP hook system. RESULTS: The screw pullout rate was 36.4% (27/74). Perioperative radiographic parameters were not significantly different between the pullout and non-pullout groups. The vertebral body HU and pedicle HU were significantly lower in the pullout group. K-means clustering stratified the vertebral body HU ≥205.3, <137.2, and pedicle HU ≥243.43, <156.03. The pullout rate significantly decreases in patients receiving the hook system when the pedicle HU was from ≥156.03 to < 243.43 (p<0.05), but the difference was not statistically significant in the vertebra HU stratified groups and when pedicle HU was ≥243.43 or <156.03. The postoperative clinical outcomes improved significantly with the implementation of the hook system. CONCLUSION: The UIV hook provides better clinical outcomes and can be considered a preventative strategy for screw-pullout in the certain pedicle HU range.

17.
Int J Mol Sci ; 25(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38203330

RESUMEN

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.


Asunto(s)
Neoplasias , Plantas Medicinales , Humanos , Pronóstico , Caquexia/etiología , Caquexia/genética , Simulación del Acoplamiento Molecular , Farmacología en Red , Perfilación de la Expresión Génica , Extractos Vegetales , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/genética
18.
Neurospine ; 20(4): 1272-1280, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38171294

RESUMEN

OBJECTIVE: Although adult spinal deformity (ASD) surgery aims to restore and maintain alignment, proximal junctional kyphosis (PJK) may occur. While existing scoring systems predict PJK, they predominantly offer a generalized 3-tier risk classification, limiting their utility for nuanced treatment decisions. This study seeks to establish a personalized risk calculator for PJK, aiming to enhance treatment planning precision. METHODS: Patient data for ASD were sourced from the Korean spinal deformity database. PJK was defined a proximal junctional angle (PJA) of ≥ 20° at the final follow-up, or an increase in PJA of ≥ 10° compared to the preoperative values. Multivariable analysis was performed to identify independent variables. Subsequently, 5 machine learning models were created to predict individualized PJK risk post-ASD surgery. The most efficacious model was deployed as an online and interactive calculator. RESULTS: From a pool of 201 patients, 49 (24.4%) exhibited PJK during the follow-up period. Through multivariable analysis, postoperative PJA, body mass index, and deformity type emerged as independent predictors for PJK. When testing machine learning models using study results and previously reported variables as hyperparameters, the random forest model exhibited the highest accuracy, reaching 83%, with an area under the receiver operating characteristics curve of 0.76. This model has been launched as a freely accessible tool at: (https://snuspine.shinyapps.io/PJKafterASD/). CONCLUSION: An online calculator, founded on the random forest model, has been developed to gauge the risk of PJK following ASD surgery. This may be a useful clinical tool for surgeons, allowing them to better predict PJK probabilities and refine subsequent therapeutic strategies.

19.
Yonsei Med J ; 63(11): 1027-1034, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36303311

RESUMEN

PURPOSE: The biplanar whole body imaging system (EOS) is a new tool for measuring the whole body sagittal alignment in a limited space. This tool may affect the sagittal balance of patients compared to conventional whole spine X-ray (WSX). This study aimed to investigate the difference in sagittal alignment between WSX and EOS. MATERIALS AND METHODS: We compared the spinal and pelvic sagittal parameters in 80 patients who underwent EOS and WSX within one month between July 2018 and September 2019. The patients were divided based on sagittally balanced and imbalanced groups according to pelvic tilt (PT) >20°, pelvic incidence-lumbar lordosis >10°, C7-sagittal vertical axis (SVA) >50 mm in WSX. RESULTS: In the sagittally imbalanced group, compared to WSX, the pelvic parameters demonstrated compensation in EOS with smaller PT (27.4±11.6° vs. 24.9±10.9°, p=0.003) and greater sacral slope (SS), and the patients tended to stand more upright with smaller C7-SVA (58.4±17.0 mm vs. 48.9±57.3 mm, p=0.018), T1-pelvic angle (TPA), T5-T12, and T2-T12. However, in the sagittally balanced group, these differences were less pronounced only with smaller PT (10.8±6.9° vs. 9.4±4.7°, p=0.040), TPA and T2-T12 angle, but with similar SS and C7-SVA (p>0.05). CONCLUSION: EOS showed a negative SVA shift and lesser PT compared to WSX, especially in patients with sagittal imbalance. When preparing a surgical plan, surgeons should consider these differences between EOS and WSX.


Asunto(s)
Cifosis , Lordosis , Humanos , Cifosis/diagnóstico por imagen , Cifosis/cirugía , Rayos X , Columna Vertebral/diagnóstico por imagen , Lordosis/diagnóstico por imagen , Radiografía , Sacro , Vértebras Lumbares
20.
Acta Neurochir (Wien) ; 164(12): 3173-3180, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36251069

RESUMEN

STUDY DESIGN: This is a retrospective study. OBJECTIVE: Implant nonfusion is an important prognostic factor for patients after anterior cervical discectomy and fusion (ACDF). This study aimed to investigate endplate-specific pseudarthrosis after ACDF, to determine if the rate of fusion is inferior in the lower endplate, and to identify any differences in clinical and radiological results. Research comparing each endplate on which the endplate affects nonfusion is limited. METHODS: We analyzed 71 patients with 142 total spinal levels who underwent double-level ACDF (C4-5-6 and C5-6-7) with an allograft and plate at our hospital between January 2012 and December 2018. Fusion grades were assessed using computed tomography and the Bridwell fusion grade system at 1 year postoperatively. Radiological parameters were obtained from lateral cervical radiographs collected preoperatively and at 1 month and 1 year after surgery. RESULTS: There was no difference in fusion between the C4-5-6 and C5-6-7 ACDF procedures, but the fusion rate and Bridwell fusion grade at the caudal surgery level were lower than those at the cranial surgery level (93 vs. 79%, p < 0.001). The lower endplate of the caudal fusion level showed the most common pseudarthrosis (18 of 71 [25%]). There was no difference in radiological parameters and clinical outcomes between the fusion and pseudarthrosis groups. CONCLUSION: In double-level ACDF procedures, the nonfusion rate was higher at the caudal fusion levels, especially at the lower endplates of the caudal fusion levels.


Asunto(s)
Seudoartrosis , Fusión Vertebral , Humanos , Seudoartrosis/diagnóstico por imagen , Seudoartrosis/etiología , Seudoartrosis/cirugía , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Fusión Vertebral/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Discectomía/métodos
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