Possible Involvement of Serum and Synovial Fluid Resistin in Knee Osteoarthritis: Cartilage Damage, Clinical, and Radiological Links.

BACKGROUND: Resistin is an adipocytokine associated with inflammation and insulin resistance. Recent studies have shown that resistin plays an important role in the pathogenesis and progression in osteoarthritis (OA) patients. The current study was aimed at investigating the relationship between resistin in serum and synovial fluid (SF) and disease severity in patients with knee osteoarthritis. METHOD: Seventy-four patients diagnosed with knee OA and 79 healthy controls receiving regular body check in our hospital were recruited in the study. The Noyes score method was used to assess articular cartilage damage arthroscopically. The symptomatic severity was evaluated according to the Western Ontario McMaster University Osteoarthritis (WOMAC) scores. The radiographic disease severity of OA was assessed by the Kellgren-Lawrence (K-L) grading system. The resistin levels in serum and SF were determined by enzyme-linked immunosorbent assay. Cartilage degradation marker CTX-II in SF was also examined. RESULTS: SF but not serum resistin levels are positively associated with Noyes scores, K-L grading scores WOMAC pain scores, physical functional scores and WOMAC total scores. In addition, SF resistin correlated positively with CTX-II. CONCLUSION: Resistin in SF might serve as a potential biomarker for reflecting the disease severity and cartilage degenerative extent of knee OA.

Increased Synovial Fluid YKL-40 Levels are Linked with Symptomatic Severity in Knee Osteoarthritis Patients.

BACKGROUND: Elevated serum and synovial fluid (SF) YKL-40 levels have been detected in knee osteoarthritis (OA) patients. The current study was focused on the correlation between YKL-40 levels in serum or SF and symptomatic severity in patients with knee osteoarthritis. METHODS: 144 patients with knee OA and 151 healthy individuals were recruited into this study. Symptomatic severity was determined using Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from OA patients. Serum and SF levels of YKL-40 were explored by enzyme-linked immunosorbent assay. RESULTS: We found that YKL-40 levels in SF but not serum were independently and positively related to WOMAC pain (r = 0.531, p = 0.001), physical disability (r = 0.380, p = 0.025), and total scores (r = 0.407, p = 0.01) in knee OA patients. CONCLUSIONS: YKL-40 in SF could represent a potential biomarker for assessing the symptomatic severity of OA.

Advance in the application of organoids in bone diseases.

Bone diseases such as osteoporosis and osteoarthritis have become important human health problems, requiring a deeper understanding of the pathogenesis of related diseases and the development of more effective treatments. Bone organoids are three-dimensional tissue masses that are useful for drug screening, regenerative medicine, and disease modeling because they may mimic the structure and physiological activities of organs. Here, we describe various potential methods for culturing bone-related organoids from different stem cells, detailing the construction processes and highlighting the main applications of these bone organoid models. The application of bone organoids in different skeletal diseases is highlighted, and current and promising bone organoids for drug screening and regenerative medicine as well as the latest technological advancements in bone organoids are discussed, while the future development of bone organoids is discussed. Looking forward, it will provide a reference for constructing bone organoids with more complete structures and functions and applying them to biomedical research.

An integration-free induced pluripotent stem cell line from a 42-year-old female donor with the APOE-ε2/ε2 allele.

The APOE 4 allele remains the primary genetic risk factor for sporadic Alzheimer's disease, whereas the APOE 2 allele emerges as a protective factor. Therapeutic approaches in murine models with human APOE alleles, such as modulating APOE levels and converting isoforms, show efficacy. However, there is a lack of in vitro APOE2-mutant human neuronal models. Hence, in this study, we generated human induced pluripotent stem cells (hiPSCs) from the peripheral blood mononuclear blood cells (PMBC) of a 42-year-old female donor carrying the APOE-ε2/ε2 allele. The newly generated hiPSC displayed normal karyotype and could differentiate into three germ layers. Besides, they retained their original genotype and expressed pluripotency markers.

Induced human pluripotent stem cells (HEBHMUi013-A) derived from a patient of sporadic Alzheimer's disease.

Sporadic Alzheimer's disease (sAD) is the most common neurodegenerative disease worldwide, which is characterized by the progressive cognitive dysfunction and behavioral impairment. Here, we generated a human induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) isolated from a 78-year-old male patient clinically diagnosed with sAD. The iPSC line expressed pluripotency markers, showed normal karyotype, and had the ability to differentiate into three germ layers in vitro. This iPSC line may provide a powerful tool for modeling AD in vitro and studying the pathogenesis of sAD.

Human induced pluripotent stem cells generated from a 45-years-old male donor of type 2 diabetes mellitus with APOE-epsilon3/epsilon3 alleles.

Apolipoprotein E (APOE) gene encodes three protein isoforms (APOEε-22/ε-33/ε-44), which governs the transportation and metabolism of lipoproteins differently. While abnormalities in lipid and lipoprotein metabolism have been identified as risk factors for type 2 diabetes mellitus (T2DM). APOE gene polymorphisms might be correlated with increased risk of T2DM. Therefore, we presented an iPSC line harboring an APOE-ε3/ε3 alleles, a male donor suffering from T2DM combined with Hypertension. The derived iPSCs showed pluripotency, the capacity to differentiate into three germ layers, and normal karyotypes. Collectively, the present study provides a useful resource to reveal the associated mechanism of APOE isoform and T2DM.

Production and validation of human induced pluripotent stem cell line from sporadic amyotrophic lateral sclerosis (SALS).

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with the loss of upper motor neurons in the cortex and lower motor neurons in the brain stem and spinal cord regressively. The vast majority of ALS cases have no familial history are apparently sporadic (SALS), making the modeling of SALS essential to the development of ALS therapeutics. Therefore, human induced pluripotent stem cell (iPSC) from peripheral blood mononuclear cells of a 64-year-old SALS patient were produced using a virus-free protocol and characterized using standard validate methods. This generated iPSC line could be useful to reveal SALS mechanisms and screen drug development.

Induced pluripotent stem cell (iPSC) line (HEBHMUi002-A) from a healthy female individual and neural differentiation.

Induced pluripotent stem cells (iPSCs) can be used to generate different types of somatic cells in vitro, including neuronal cells. Here, a human iPSC line was generated from the peripheral blood mononuclear cells of a healthy 39-year-old individual. The resulting iPSCs were integration-free, maintained the normal karyotype, expressed pluripotency stem cell markers, and were demonstrated to be capable of differentiating into cells representative of the three embryonic germ layers. Furthermore, we showed that this iPSC line could be differentiated into neural stem cells. Taken together, this generated iPSC line could be useful to test multiple differentiation protocols, and also serve as a control for investigating drug development and disease mechanisms.

Induced pluripotent stem cell line derived from a sporadic amyotrophic lateral sclerosis patient.

Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) obtained from a 60-year-old female diagnosed with sporadic amyotrophic lateral sclerosis (sALS). The iPSCs shared the same karyotype with the parent PBMCs, expressed pluripotency stem cell markers, and demonstrated trilineage differentiation potential. This cell line could serve as an ideal model to investigate the mechanisms underlying amyotrophic lateral sclerosis (ALS).

Long noncoding RNA LINC00314 facilitates osteogenic differentiation of adipose-derived stem cells through the hsa-miR-129-5p/GRM5 axis via the Wnt signaling pathway.

BACKGROUND: Many studies have shown that long noncoding RNAs (lncRNAs) are closely related to the stimulation of osteogenic differentiation of adipose-derived stem cells (ADSCs) and the prevention of osteoporosis. Current research aimed to investigate the novel lncRNA and explored the function and molecular mechanism of the LINC00314/miR-129-5p/GRM5 axis in regulating osteogenic differentiation of ADSCs. METHODS: LncRNA and miRNA sequencing was performed in normal and osteogenic differentiation-induced ADSCs (osteogenic group). Abnormally expressed lncRNAs and miRNAs were obtained by the R software and the relative expression of LINC00314, miR-129-5p, and GRM5 during osteogenic induction was measured by RT-PCR. ADSCs were then transfected with pcDNA3.1-sh-LINC00314 and agomiR-129-5p. Alizarin red staining (ARS) and alkaline phosphatase (ALP) staining were performed to identify the mechanism of the LINC00314/miR-129-5p/GRM5 axis in regulating osteogenic differentiation of ADSCs. RESULTS: LINC00314 was significantly upregulated in the group of osteogenic-induced ADSCs. LINC00314 and GRM5 mimics increased the early and late markers of osteogenic differentiation, which manifest in not only the markedly increased ALP activity but also higher calcium deposition, while miR-129-5p mimic had the opposite effects. LINC00314 directly targeted miR-129-5p through luciferase reporter assay, and miR-129-5p suppressed GRM5 expression. Moreover, the LINC00314/miR-129-5p/GRM5 regulatory axis activated the Wnt/ß-catenin signaling pathway. CONCLUSIONS: LINC00314 confers contributory function in the osteogenic differentiation of ADSCs and thus the LINC00314/miR-129-5p/GRM5 axis may be a novel mechanism for osteogenic-related disease.

Generation and characterization of a human induced pluripotent stem cell (iPSC) line (HEBHMUi001-A) from a sporadic Parkinson's disease patient.

We generated a human induced pluripotent stem cell (iPSC) line from the skin fibroblasts of a 62-year-old female patient clinically diagnosed with sporadic Parkinson's disease (PD). The generated iPSCs maintained their normal karyotype, expressed pluripotency stem cell markers, and were demonstrated to be capable of differentiating into cells representative of the three embryonic germ layers. The generated line could be used for PD modeling in order to understand the mechanisms that influence the disorder.

[Clinical significance of expression of PSA, hK2, PSMA in the peripheral blood of patients with prostate cancer].

OBJECTIVE: To find sensitive and specific micro-metastic markers for prostate cancer. METHODS: Using nested reverse transcription-PCR, we examined the expression of PSA, hK2 and PSMA mRNA in peripheral blood mononuclear cells of 51 patients with prostate cancer, 33 patients with benign prostate hyperplasia (BPH) and 32 normal young people. RESULTS: The expression rates of PSA, hK2 and PSMA mRNA were 52.9%, 43.1% and 64.7%, respectively in prostate cancer group, and 6.2%, 7.7% and 4.6%, respectively in control group (BPH patients and normal young people) with statistical significance (P < 0.01). Although the expression rate of PSA and hK2 mRNA increased with cancer progression, there was no statistical significance among patients in different stages. The expression rate of PSMA mRNA was higher than that of PSA and hK2 mRNA in each clinical stage. CONCLUSION: PSMA mRNA expression detected by nested RT-PCR is of greater value for the diagnosis, therapy choice and prognostic evaluation of prostate cancer patients.