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Background: In microsurgical tissue transfer, skin flap transplantation is frequently used to heal the surface of a wound. Effective microcirculation surveillance of the skin flap is crucial. However, with traditional monitoring methods-that is, clinical observation-vascular crisis can still occur, thereby impairing postoperative recovery. A smartphone application is required to assist health care professionals in the standardized collection of flap perfusion parameters for flap management. Methods: The Vascular Crisis Prewarning Application was created using a design science research methodology that prioritizes users and problems. The system usability scale was used to assess the application's usability among medical practitioners. The application was used at the clinic from December 2020 to September 2022. The unplanned return to the operating room, time to diagnose vascular crisis, and flap survival rate were compared with and without the application. Results: The application consisted of 5 modules: patient addition and basic information entry, flap labeling, flap observation, crisis warning, and case archiving. The average rating for the application's usability among medical practitioners was 97.95 score (SD 2.36). With the application, the time to detect vascular crisis reduced from 26.71 to 16.26 h (P < 0.001), the unplanned return to the operation room increased from 8.18% to 10.24% (P = 0.587), and the flap survival rate went from 94.55% to 99.21% (P = 0.083). Conclusions: An easy-to-use flap perfusion monitoring and prewarning application for medical practitioners was produced using a user-centered development method. The application provided a more standardized and accurate platform for data collection in flap management and reduced the time to detect vascular crisis. Larger cohort studies are required in the future to better assess the full potential of the application.
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BACKGROUND: Traumatic tibial defect complicated with soft tissue defect is a difficult problem in clinic. Vascularized iliac crest bone flap (VIBF) and Ilizarov bone transport are effective methods to treat tibial defects with limited defect length, which most need to be explored accordingly. METHODS: In this study, a total of 68 patients with traumatic tibial defect (ranging from 4 to 10 cm) and large soft tissue defect were collected retrospectively. The soft tissue defects were repaired by latissimus dorsal musculocutaneous flap (LD), anterolateral thigh flap (ALTF) or both. Thirty-three cases were treated with vascularized iliac crest bone flap transplantation and 35 cases were treated with Ilizarov bone transport. Intraoperative and postoperative follow-up data (including operation time, blood loss, bone union time, external fixation time, external fixation index, complication rate, reoperation rate, and functional evaluation) were recorded, and comparative analysis was performed. RESULTS: The median follow-up time was 32 months. Compared with Ilizarov group, the VIBF group exhibited statistically faster bone union time (6.3 ± 1.0 vs. 18.2 ± 3.0 months). Moreover, the VIBF group showed shorter EFT (7.3 ± 1.0 vs. 19.2 ± 3.0 months) and a better EFI (34.8 ± 9.2 vs. 84.2 ± 23.7 days/cm). The excellent and good rate of lower limb appearance evaluation in VIBP group was significantly better than that in Ilizarov group. The complication rate and reoperation rate were significantly higher in Ilizarov group. CONCLUSION: In summary, compared with Ilizarov bone transport, VIBP has the advantages of faster healing, shorter external fixation time, lower complication and reoperation rate, and better appearance within the limited defect length. Ilizarov bone transport is still preferred when the defect length exceeds the maximum repair length of the iliac flap. The daily handling required by bone transport process is painful. LEVEL OF EVIDENCE: III, Case-control study.
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Técnica de Ilizarov , Fracturas de la Tibia , Humanos , Tibia/cirugía , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Ilion , Estudios Retrospectivos , Estudios de Casos y Controles , Resultado del TratamientoRESUMEN
Background: Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis affecting children. The lack of effective and timely treatment results in severe sequelae in children (especially older ones). Although LCPD has been widely studied, little is known about its etiology. As a result, its clinical management is still challenging. This study will investigate the clinical and radiological results of patients older than 6 years and treated with pedicled iliac bone flap grafting for LCPD. Materials and methods: A total of 13 patients (13 hips) with late presentation of LCPD were treated with pedicled iliac bone flap grafting. Of the 13 patients, 11 were male and 2 were female. The average age of the patients was 8.4 years (range 6-13). Preoperational radiographs and pain scores were analyzed for lateral pillar classification and the Oucher scale. The final follow-up radiograph was classified using a modified Stulberg classification. Limping, extremity length inequality, and range of motion were clinically assessed. Results: The average follow-up of the patients was 70 months (range 46-120). During the surgery, seven hips were found to be lateral pillar grade B, two were grade B/C, and four were grade C. In the final examination, 12 hips were evaluated as good (Stulberg class I or II) and one as medium (Stulberg class III). There was limb shortening in one patient who was Stulberg class III. There was a significant difference between the preoperational and postoperational radiographic values and the Ocher scale, regardless of the surgical staging (P < 0.05). Conclusions: Pedicled iliac bone flap graft can treat LCPD accompanied by pain and lateral pillar stage B, B/C, and C in children over 6 years. Level of Evidence: Level IV-case series.
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Preaxial polydactyly (PPD) is a common congenital abnormality with an incidence of 0.8-1.4% in Asians, characterized by the presence of extra digit(s) on the preaxial side of the hand or foot. PPD is genetically classified into four subtypes, PPD type I-IV. Variants in six genes/loci [including GLI family zinc finger 3 (GLI3), ZPA regulatory sequence (ZRS), and pre-ZRS region] have been identified in PPD cases. Among these loci, ZRS is, perhaps, the most special and well known, but most articles only reported one or a few cases. There is a lack of reports on the ZRS-variant frequency in patients with PPD. In this study, we recruited 167 sporadic or familial cases (including 154 sporadic patients and 13 families) with PPD from Central-South China and identified four ZRS variants in four patients (2.40%, 4/167), including two novel variants (ZRS131A > T/chr7:g.156584439A > T and ZRS474C > G/chr7:g.156584096C > G) and two known variants (ZRS428T > A/chr7:g.156584142T > A and ZRS619C > T/chr7:g.156583951C > T). ZRS131A > T and ZRS428T > A were detected in PPD I cases and ZRS474C > G and ZRS619C > T combinedly acted to cause PPD II. The detectable rate of ZRS variants in PPD I was 1.60% (2/125), while PPD II was significantly higher (9.52%, 2/21). Three bilateral PPD cases harbored ZRS variants (13.64%, 3/22), suggesting that bilateral PPD was more possibly caused by genetic etiologies. This study identified two novel ZRS variants, further confirmed the association between ZRS and PPD I and reported a rare PPD II case resulted from the compound heterozygote of ZRS. This investigation preliminarily evaluated a ZRS variants rate in patients with PPD and described the general picture of PPD in Central-South China.
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Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC50 values in the range of 0.03-8.40â µM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines.
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Aglaia , Antineoplásicos Fitogénicos , Antineoplásicos , Triterpenos , Aglaia/química , Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Dicroismo Circular , Humanos , Estructura Molecular , Extractos Vegetales/química , Triterpenos/químicaRESUMEN
The novel composite, Fe3O4@SiO2@mSiO2-PW12/Ag, was successfully prepared by in situ loading Ag nanoparticles (Ag NPs) on the surface of grafted phosphotungstate (denoted as PW12) Fe3O4@SiO2@mSiO2via a photoreduction deposition method. PW12 not only acts as a reducing agent and stabilizer for Ag NPs but also as a bridge to link Ag NPs and the SiO2 shell in the loading process. Its activity toward the photodegradation of methyl orange (MO) and photoreduction of Cr2O72- anions was evaluated. Experimental results showed that Fe3O4@SiO2@mSiO2-PW12/Ag with 5.3 wt% Ag loading and 18.65 wt% of PW12 exhibits the highest photocatalytic efficacy, and complete degradation of MO and 91.2% photoreduction of Cr(vi) were realized under simulated sunlight for 75 min, respectively. The enhanced catalytic activities of the composite are due to its high specific surface area, the synergistic effect among the components and the formation of a heterojunction of PW12/Ag. The possible enhanced photocatalytic mechanism is proposed. The catalyst is durable and can be easily recovered using a magnet for recycling without a significant loss of catalytic activity.
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Background: Preaxial polydactyly (PPD) is one of the most common developmental malformations, with a prevalence of 0.8-1.4% in Asians. PPD is divided into four types, PPD I-IV, and PPD I is the most frequent type. Only six loci (GLI1, GLI3, STKLD1, ZRS, pre-ZRS, and a deletion located 240 kb from SHH) have been identified in non-syndromic PPD cases. However, pathogenesis of most PPD patients has never been investigated. This study aimed to understand the genetic mechanisms involved in the etiology of PPD I in a family with multiple affected members. Methods: We recruited a PPD I family (PPD001) and used stepwise genetic analysis to determine the genetic etiology. In addition, for functional validation of the identified GLIS1 variant, in vitro studies were conducted. GLIS1 variants were further screened in additional 155 PPD cases. Results: We identified a GLIS1 variant (NM_147193: c.1061G > A, p.R354H) in the PPD001 family. In vitro studies showed that this variant decreased the nuclear translocation of GLIS1 and resulted in increased cell viability and migration. RNA sequencing revealed abnormal TBX4 and SFRP2 expression in 293T cells transfected with mutant GLIS1. Additionally, we identified a GLIS1 variant (c.664G > A, p.D222N) in another PPD case. Conclusion: We identified two GLIS1 variants in PPD I patients and first linked GLIS1 with PPD I. Our findings contributed to future molecular and clinical diagnosis of PPD and deepened our knowledge of this disease.
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Background: Hereditary sensory and autonomic neuropathies (HSANs) are a rare and severe group of sensory axonal neuropathies. HSANs have been classified into eight groups based on mode of inheritance, clinical features, and the involved genes. HSAN-VI, perhaps the most notable type, is an autosomal recessive disease, which manifests as the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and sometimes early death. Mutations in DST have been identified as the cause of HSAN-VI. DST encodes dystonin, a member of the plakin protein family that is involved in cytoskeletal filament networks. Dystonin has seven major isoforms in nerve, muscle, and epithelium. Material and Methods: The present study investigated a Chinese family with HSAN and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of variant pathogenicity. Co-segregation analysis was subsequently conducted. Results: We identified compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients. Conclusion: We reported on a Chinese family with HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.
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Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. This study aimed to determine whether EVs from human urine-derived stem cells (USC-EVs) could protect against GC-induced ONFH and focused on the impacts of USC-EVs on angiogenesis and apoptosis to explore the mechanism by which USC-EVs attenuated GC-induced ONFH. The results in vivo showed that the intravenous administration of USC-EVs at the early stage of GC exposure could rescue angiogenesis impairment, reduce apoptosis of trabecular bone and marrow cells, prevent trabecular bone destruction and improve bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reversed the GC-induced suppression of endothelial angiogenesis and activation of apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) proteins were enriched in USC-EVs and essential for the USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 attenuated the protective effects of USC-EVs against GC-induced ONFH. Our study suggests that USC-EVs are a promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1. STATEMENT OF SIGNIFICANCE: This study demonstrates that the intravenous injection of extracellular vesicles from human urine-derived stem cells (USC-EVs) at the early stage of glucocorticoid (GC) exposure efficiently protects the rats from the GC-induced osteonecrosis of the femoral head (ONFH). Moreover, this study identifies that the promotion of angiogenesis and inhibition of apoptosis by transferring pro-angiogenic DMBT1 and anti-apoptotic TIMP1 proteins contribute importantly to the USC-EVs-induced protective effects against GC-induced ONFH. This study suggests the promising prospect of USC-EVs as a new nano-sized agent for protecting against GC-induced ONFH, and the potential of DMBT1 and TIMP1 as the molecular targets for further augmenting the protective function of USC-EVs.
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Vesículas Extracelulares , Osteonecrosis , Animales , Proteínas de Unión al Calcio , Proliferación Celular , Proteínas de Unión al ADN , Cabeza Femoral , Glucocorticoides , Humanos , Ratas , Células Madre , Inhibidor Tisular de Metaloproteinasa-1 , Proteínas Supresoras de TumorRESUMEN
Four new sesquiterpenoids, phellinignins A-D (1-4), together with four known ones (5-8), were isolated from cultures of the fungus Phellinus igniarius. The structures were established by extensive spectroscopic methods including MS, NMR, and the single crystal X-ray diffraction. Compounds 1-3 and 5-8 are tremulane sesquiterpenoids, while compound 4 possesses a new carbon skeleton that might derive from an illudane framework. Compounds 1, 2, 4, and 5 showed certain cytotoxicities to three human cancer cell lines.
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Antineoplásicos/farmacología , Basidiomycota/química , Sesquiterpenos/farmacología , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , China , Humanos , Estructura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/aislamiento & purificaciónRESUMEN
BACKGROUNDS: Due to the delicate tissue, small blood vessels and incomplete development of interarticular ligaments, skin and soft-tissue defects of the foot and ankle in pediatric patients remain a challenge for orthopedic and plastic surgeons. Anterolateral thigh perforator (ALTP) flap and deep inferior epigastric perforator (DIEP) flap are the most commonly used flaps for the repair of lower-extremity soft-tissue defects. The literature contains a shortage of evidence involving the differences between ALTP and DIEP flaps in the reconstruction of young patients with complex foot and ankle defects. This study was designed to determine which type of flap is better for foot and ankle repair in pediatric patients. METHODS: From January 2004 to January 2018, 79 children younger than 14 years treated with DIEP flap (41 cases) or ALTP flap (38 cases) for composite defects of the feet and ankles were retrospectively investigated. The two groups were homogeneous in terms of age, the location of the defect, etiology, and flap area. Complications, scarring, cosmetic appearance, flap sensory recovery, and functional outcome were analyzed, and statistical analysis was performed. RESULTS: The ALTP group had shorter operation time (155.0⯱â¯12.0â¯min vs 212.2⯱â¯23.9â¯min), flap harvested time (39.6⯱â¯5.1â¯min vs 57.2⯱â¯10.4â¯min), and operative blood loss (143.4⯱â¯23.7â¯ml vs 170.7⯱â¯44.7â¯ml) than the DIEP group (Pâ¯<⯠0.05). In short-term follow-up, ALTP group showed a lower flap necrosis rate (5.3% vs 24.4%) and vascular insufficiency rate (2.6% vs 19.5%) than DIEP group (Pâ¯<⯠0.05). In long-term follow-up, ALTP group showed a lower late complication rate and better cosmetic, functional, scar outcomes than DIEP group (Pâ¯<⯠0.05). CONCLUSIONS: The study showed that an ALTP flap may brings better results than a DIEP flap in terms of short- and long-term complications, scarring, and morpho-functional outcomes for pediatric patients undergoing reconstruction of foot and ankle defects.
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Traumatismos del Tobillo/cirugía , Traumatismos de los Pies/cirugía , Supervivencia de Injerto/fisiología , Colgajo Perforante/irrigación sanguínea , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos/cirugía , Traumatismos del Tobillo/fisiopatología , Preescolar , Desbridamiento , Femenino , Traumatismos de los Pies/fisiopatología , Humanos , Masculino , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Trasplante de Piel/métodos , Traumatismos de los Tejidos Blandos/fisiopatología , Muslo/cirugía , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
OBJECTIVE: Mucolipidosis II and III alpha/beta (ML II & ML III alpha/beta) are rare autosomal recessive lysosomal storage disorders. ML II is clinically evident from birth with a progressive course and fatal outcome in childhood. The typical phenotypes of ML II include limited statural growth, craniofacial abnormality, skeletal malformation, intelligence developmental deficiency and visceral organ abnormality. ML III is milder than ML II. Mutations in GNPTAB cause the ML II/III. METHODS: Two families with ML II/III (initially undiagnosed) were recruited. We applied whole-exome sequencing (WES) and filtered mutations by genes causing lysosomal storage diseases with skeletal involvement. Mutational analysis and co-segregation confirmation were then performed. RESULTS: We presented two families with ML II or ML III alpha/beta. By WES, the compound heterozygosity of GNPTAB (c.2404C>T, p.Q802* and c.2590dup, p.E864Gfs*4) is identified in a family with ML II, and c.1364C>T, p.A455V and c.2715+1G>A are detected in a family with ML III alpha/beta. CONCLUSION: We detected the causative mutations in two ML II/III families by WES and confirmed their diagnosis of the diseases. The present identification of mutations expands the spectrum of known GNPTAB mutations and it may contribute to novel approaches to genetic diagnosis and counseling for patients with ML II/III.
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BACKGROUND: This study investigates the feasibility and clinical impact of the microdissected thin perforator skin flap strategy on bulky and deformed skin flaps during second-stage revision surgery. METHODS: Seventeen patients were selected and underwent the microdissected thin perforator skin flap technique to treat bulky and deformed skin flaps after free flap reconstruction between October 2013 and October 2015. Perforator vessels were isolated and protected under a microscope. Subdermal fat with a thickness of 4 mm to 7 mm was preserved, and excess adipose tissue was resected. RESULTS: No skin flap necrosis was observed after the operation in all 17 patients, and all wounds healed without complications. Patients were followed up for 3 to 24 months, with an average follow-up time of 10 months. The skin flaps maintain normal color and texture. Both appearance and function of the recipient sites were improved significantly. CONCLUSIONS: The utilization of microdissected thin perforator flap technique to further thin bulky skin flaps at the second stage can be effective in a single operation. The blood supply of all free flaps was preserved, with no evidence of necrosis or healing complications. This technique offers an effective approach for secondary thinning of bulky free flaps.
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Colgajo Perforante/irrigación sanguínea , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/cirugía , Trasplante de Piel/métodos , Adolescente , Adulto , Niño , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Resultado del Tratamiento , Ultrasonografía Doppler , Cicatrización de HeridasRESUMEN
Werner Syndrome (WS) is a rare, adultonset progeroid syndrome that is associated with multiple ageassociated complications and relatively short life expectancy. The characteristics of WS include a 'birdlike' appearance, canities, cataracts and ulcerations around the ankles. In addition, certain patients develop hypogonadism with atrophic genitalia and infertility. The average life span of affected individuals is 54 years. Previous studies have demonstrated that mutations in the Werner syndrome RecQ like helicase gene (WRN) may contribute to WS. The present study investigated a consanguineous family with WS, comprising of 4 generations from Northwest China (Gansu province). A novel homozygous splicesite mutation in WRN (c.IVS28+2T>C) was identified in this family and was predicted to be deleterious. No further relevant mutations were identified by direct sequencing of the genes lamin A/C, barrier to autointegration factor 1, zinc metallopeptidase STE24 and DNA polymerase Δ1. cDNA sequencing and alignments were performed to further confirm the pathogenicity of this mutation. The results support the important role of WRN in WS and expand the spectrum of known WRN mutations. In addition, it may provide novel approaches in genetic diagnosis and counseling of families with WS.
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Mutación , Sitios de Empalme de ARN , Helicasa del Síndrome de Werner/genética , Síndrome de Werner/diagnóstico , Síndrome de Werner/genética , Alelos , Consanguinidad , Análisis Mutacional de ADN , Femenino , Homocigoto , Humanos , Masculino , Linaje , FenotipoRESUMEN
BACKGROUND: Distal arthrogryposis (DA) is the most common congenital limb malformation secondary to the functional defects of joints and muscles. DA1 is one of the most commonly described forms of DA. The characteristics of DA1 include bilateral and symmetric clenched fist, overlapping fingers, camptodactyly, ulnar deviation of fingers, and positional foot deformities such as talipes equinovarus. Previous studies demonstrate that mutations of TPM2, TNNI2, TNNT3, MYH3 and MYBPC1 may contribute to DA1. MATERIALS AND METHODS: The present study investigated 8 DA1 families/patients and 1 DA2B patient, determined sequences of TPM2, TNNI2, TNNT3, MYH3 and MYBPC1 and detected the mutation by multiple sequence alignments and bioinformatic prediction of mutation. RESULTS: We identified a novel missense mutation of TPM2 (c.463G>A; p.A155T) in a DA1 family without genetic mutant of TNNI2, TNNT3, MYH3 and MYBPC1. CONCLUSION: The mutation of TPM2 (c.463G>A; p.A155T) led to DA1 of the family. The identification of the mutation expands the spectrum of known TPM2 mutations, and it may contribute to novel approaches to genetic diagnosis and counseling of families with DA1.
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Preaxial polydactyly (PPD; OMIM 603596), which is characterized as having supernumerary fingers, is an unusual congenital hand abnormality. Triphalangeal thumb (TPT; OMIM 190600) is identified by an extra phalangeal bone and is often found in association with PPD. When in combination, the disease is referred to as PPD type II (PPD II; OMIM 174500). Previous studies have demonstrated that variations in the zone of polarizing activity regulatory sequence (ZRS; chr7:156,583,796-156,584,569; hg19) region are associated with PPD II. In this study, our patient was diagnosed with PPD II, having bilateral thumb duplication and unilateral TPT (on the right hand). Further investigation of possible causative genes identified a de novo heterozygous ZRS mutation (ZRS 428T>A). This novel mutation was neither found in 200 normal controls nor reported in online databases. Moreover, the bioinformatics program Genomic Evolutionary Rate Profiling (GERP) revealed this site (ZRS428) to be evolutionarily highly conserved, and the 428T>A point mutation was predicted to be deleterious by MutationTaster. In conclusion, the affected individual shows bilateral thumb duplication, but unilateral TPT making this case special. Thus, our findings not only further support the important role of ZRS in limb morphogenesis and expand the spectrum of ZRS mutations, but also emphasize the significance of genetic diagnosis and counseling of families with digit number and identity alterations as well.
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Pueblo Asiatico/genética , Deformidades Congénitas de la Mano/genética , Proteínas de la Membrana/genética , Mutación Puntual/genética , Polidactilia/genética , Pulgar/anomalías , China , Heterocigoto , Humanos , LactanteRESUMEN
OBJECTIVES: miR-125b has been identified as a tumor suppressor in many tumors, but its role in giant cell tumor (GCT) of bone remains poorly understood. The current study aimed to investigate the potential role and mechanism of miR-125b in GCT. MATERIALS AND METHODS: Expression levels of miR-125b in GCT tissues were determined using RT-PCR. The cell proliferation was surveyed by direct cell counting, MTS and CCK-8, and the apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining assay. The target gene expression was determined using RT-PCR and western blot. Parathyroid hormone 1 receptor (PTH1R) 3'-UTR was cloned into luciferase reporter plasmid to confirm direct targeting. RESULTS: We found that miR-125b was significantly down-regulated in GCT tissues. Using both gain- and loss-of-function analyses, we further revealed that miR-125b suppressed GCT stromal cell proliferation and induced cell apoptosis. Furthermore, we revealed that PTH/PTHrP type 1 receptor is a direct and functional target of miR-125b. CONCLUSION: Our results suggest that miR-125b acts as a tumor suppressor through suppression of the PTH1R/RANKL signaling pathway. These findings contribute to our understanding of the functions of miR-125b in GCT.
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Objective. The effects of Flos Puerariae extract (FPE) on cognitive impairment associated with diabetes were assessed in C57BL/6J mice. Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ) for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA) and total cholesterol (TCH) in serum, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in cerebral cortex and hippocampus were also measured. Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE. Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.
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Giant cell tumor is a relatively uncommon but painful tumor of bone, which can metastasize to the lungs. The RANK pathway is often reported to be involved in the pathogenesis of giant cell tumor of bone (GCTB). This pathway is a key signaling pathway of bone remodeling that plays a critical role in differentiation of precursors into multinucleated osteoclasts, and activation of osteoclasts leading to bone resorption. Dysregulation of RANK ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling cascade induces the imbalance between bone formation and bone resorption, which leads to the changes in bone mass, increases osteoclast-mediated bone destruction, bone metastasis, and the progression of existing skeletal tumors. Recent evidences have shown that targeting the components of RANKL-RANK-OPG signaling pathway is a promising approach in the treatment of GCTB. This review study has focused on the association of RANKL-RANK-OPG pathway in the pathogenesis and progression of GCTB as well as discussed the possible therapeutic strategies by targeting this pathway.