To optimize the most efficient method for porcine in vitro maturation (IVM), we compared the effects of supplementing extracellular vesicles (EVs) derived from porcine follicular fluid (pFF). The cumulus oocyte complexes were grouped into 4 groups with different supplementations as following: pFF (G1), pFF-depleted EVs (G2), EVs (G3) and control (G4) groups. After IVM with different supplementations, maturation rates and the developmental competences of porcine oocytes and blastocyst development were investigated. Additionally, glutathione (GSH) and reactive oxygen species (ROS) levels were measured in mature oocytes. The EVs were isolated and characterized with cryo-TEM and nanoparticle tracking analysis. The pFF significantly affected the maturation rate, whereas the presence of EVs did not show notable difference in the maturation rates. Although there were numerical increases in the measured parameters in EV and pFF-depleted EVs groups, no significant differences were observed between them. The EV group showed similar oocyte maturation rate for both positive and negative control groups. The GSH was not different among the groups, but ROS levels were significantly lower in pFF-supplemented group when compared with other groups with the highest level in the control group. G2 group wasn’t significantly different G1 and G3 group. G3 group wasn’t significantly different from G2 and G4 group. This suggests that EVs in IVM medium which probably effected partially to protect against oxidative stress and potentially enhance the quality of oocytes. This study indicates that the EVs in pFF play a significant role in improving the efficiency of oocyte maturation in porcine.

Purpose: The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling. Materials and Methods: The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection. Results: HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group. Conclusion MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

Background: The Harris-Galante (HG) prosthesis is a first-generation, cementless total hip arthroplasty (THA) prosthesis. Considering the recent increase in the demand for THA in young patients and their life expectancy, a study with a follow-up duration of longer than 20 years in a young population is needed. Therefore, we evaluated the long-term clinical and radiographic results after cementless THA using the HG prosthesis in patients younger than 50 years. Methods: A total of 61 THAs performed using the HG with a minimum follow-up of 10 years were included. There were 38 men and 11 women with an average age of 46 years and the mean follow-up duration was 22 years. Clinical evaluation included modified Harris Hip Score (HHS) and radiographic analysis consisted of cup inclination, anteversion angle, component stability, osteolysis, liner wear rate, wear-through, liner dissociation, and heterotopic ossification. Complications included recurrent dislocation, periprosthetic femoral fracture, and periprosthetic joint infection. Survivorship analysis included cup and stem revision for aseptic loosening, as well as any revision. Results: The HHS improved from 46.5 preoperatively to 81.8 postoperatively (p < 0.001). The average linear wear rate was 0.36 mm/yr. A total of 34 hips (56%) were revised: stem revision in 10 (16.4%), cup revision in 9 (14.8%), exchange limited to bearing surface in 8 (13.1%), and revision of all components in 7 (11.5%). Estimated survivorship at 34 years postoperatively was 90.9% for cup revision for aseptic loosening, 80.5% for stem revision for aseptic loosening, and 22.1% for any revision. Conclusions THA using the HG prosthesis showed satisfactory estimated survivorship of the acetabular and femoral components at 34 years postoperatively with good clinical outcomes. Bearing-related problems, such as osteolysis and liner dissociation, accounted for 56% of revision operations and were concerns in patients younger than 50 years.

Three-dimensional (3D) printing is increasing gradually in orthopedic surgery. Currently, the use of 3D printing in hip surgery is as follows: a bone model for preoperative planning or simulation, patient-specific instruments, surface treatment for stable fixation of implant, and customized implants tailored to the patient’s anatomical characteristics. Orthopedic surgeons can utilize 3D printing technology to improve the surgical techniques, minimize complications during surgery, and provide implants that are more suitable for patients in the correct position. In recent years, new materials for 3D printing are being explored, and the efficiency of cost and production time is improved by developing the production process. In addition, constant drug delivery by improving surface treatment, fusion with other new technologies, such as augmented reality, and tissue or organ regeneration using 3D bioprinting technology is being actively conducted. Above all, orthopedic surgeons should strive to provide the best treatment to patients by learning and researching these new trends, not just adhering to existing treatment methods.

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named “common factor” in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.
Humans ; Immunotherapy ; Metabolism ; Neoplasm Metastasis ; Phenotype ; Transcription Factors ; Vaccination

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named “common factor” in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.

BACKGROUND: Hip fracture surgery (HFS) is often associated with perioperative blood loss, and it frequently necessitates transfusion. However, the hemoglobin (Hb) threshold for transfusion remains controversial in hip fracture patients. We evaluated the usefulness of the restrictive strategy and preoperative intravenous iron supplementation in HFS. METHODS: We retrospectively reviewed the medical records of 1,634 patients (> 60 years of age) who underwent HFS between May 2003 and June 2014 and were followed up for 1 year or more after surgery. We used the liberal transfusion strategy until May 2009 to determine the transfusion threshold; afterwards, we switched to the restrictive transfusion strategy. Patients with the restrictive transfusion strategy (restrictive group) received intravenous iron supplementation before surgery. We compared the transfusion rate, morbidity, and mortality of the restrictive group with those of the patients with the liberal transfusion strategy (liberal group). RESULTS: Preoperative intravenous iron supplementation was not associated with any adverse reactions. The transfusion rate was 65.3% (506/775) in the liberal group and 48.2% (414/859) in the restrictive group (p < 0.001). The mean hospital stay was shorter in the restrictive group (21.5 vs. 28.8 days, p < 0.001). There was no significant difference in the postoperative medical complications including myocardial infarction and cerebrovascular event. Mortality at postoperative 30, 60, and 90 days was similar between the two groups. CONCLUSIONS: Our blood management protocol involving restrictive strategy combined with preoperative intravenous iron supplementation appears to be effective and safe in HFS of elderly patients.
Aged ; Hip Fractures ; Hip ; Humans ; Iron ; Length of Stay ; Medical Records ; Mortality ; Myocardial Infarction ; Retrospective Studies

Recently, atypical femoral fractures (AFFs) have been found in patients who were prescribed bisphosphonate to prevent osteoporotic fractures. Although the occurrence of AFF is rare, there are some concerns, such as a higher risk of delayed or non-union of AFF. This paper reviews the treatment of AFF and suggests some considerations during surgery.
Femoral Fractures ; Humans ; Osteoporosis ; Osteoporotic Fractures ; Teriparatide

OBJECTIVE: To elucidate the effect of a 12-week horizontal vibration exercise (HVE) in chronic low back pain (CLBP) patients as compared to vertical vibration exercise (VVE). METHODS: Twenty-eight CLBP patients were randomly assigned to either the HVE or VVE group. All participants performed the exercise for 30 minutes each day, three times a week, for a total of 12 weeks. Altered pain and functional ability were evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI), respectively. Changes in lumbar muscle strength, transverse abdominis (TrA) and multifidus muscle thicknesses, and standing balance were measured using an isokinetic dynamometer, ultrasonography, and balance parameters, respectively. These assessments were evaluated prior to treatment, 6 weeks and 12 weeks after the first treatment, and 4 weeks after the end of treatment (that is, 16 weeks after the first treatment). RESULTS: According to the repeated-measures analysis of variance, there were significant improvements with time on VAS, ODI, standing balance score, lumbar flexor, and extensor muscle strength (all p < 0.001 in both groups) without any significant changes in TrA (p=0.153 in HVE, p=0.561 in VVE group) or multifidus (p=0.737 in HVE, p=0.380 in VVE group) muscle thickness. Further, there were no significant differences between groups according to time in any of the assessments. No adverse events were noticed during treatment in either group. CONCLUSION: HVE is as effective as VVE in reducing pain, strengthening the lumbar muscle, and improving the balance and functional abilities of CLBP patients. Vibrational exercise increases muscle strength without inducing muscle hypertrophy.
Humans ; Hypertrophy ; Low Back Pain* ; Muscle Strength ; Paraspinal Muscles ; Ultrasonography ; Vibration* ; Visual Analog Scale

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1beta and interferon-gamma levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.
Animals ; Asthma/*chemically induced/pathology ; Female ; Inflammation/*chemically induced/pathology ; Interferon-gamma/analysis ; Interleukins/analysis ; Lung/drug effects/*pathology ; Mice, Inbred BALB C ; Nanoparticles/*adverse effects/chemistry ; Ovalbumin/adverse effects ; Polyethylene Glycols/adverse effects/chemistry ; Silicon Dioxide/*adverse effects/chemistry ; Surface Properties