Deciphering the role of apoptosis signature on the immune dynamics and therapeutic prognosis in breast cancer: Implication for immunotherapy.

Background: In breast cancer oncogenesis, the precise role of cell apoptosis holds untapped potential for prognostic and therapeutic insights. Thus, it is important to develop a model predicated for breast cancer patients' prognosis and immunotherapy response based on apoptosis-related signature. Methods: Our approach involved leveraging a training dataset from The Cancer Genome Atlas (TCGA) to construct an apoptosis-related gene prognostic model. The model's validity was then tested across several cohorts, including METABRIC, Sun Yat-sen Memorial Hospital Sun Yat-sen University (SYSMH), and IMvigor210, to ensure its applicability and robustness across different patient demographics and treatment scenarios. Furthermore, we utilized Quantitative Polymerase Chain Reaction (qPCR) analysis to explore the expression patterns of these model genes in breast cancer cell lines compared to immortalized mammary epithelial cell lines, aiming to confirm their differential expression and underline their significance in the context of breast cancer. Results: Through the development and validation of our prognostic model based on seven apoptosis-related genes, we have demonstrated its substantial predictive power for the survival outcomes of breast cancer patients. The model effectively stratified patients into high and low-risk categories, with high-risk patients showing significantly poorer overall survival in the training cohort and across all validation cohorts. Importantly, qPCR analysis confirmed that the genes constituting our model indeed exhibit differential expression in breast cancer cell lines when contrasted with immortalized mammary epithelial cell lines. Conclusion: Our study establishes a groundbreaking prognostic model using apoptosis-related genes to enhance the precision of breast cancer prognosis and treatment, particularly in predicting immunotherapy response.

SOX2 suppresses osteoblast differentiation of MC3T3-E1 cells through activating the transcription of LGR4.

Osteogenic differentiation is a crucial process of new bone formation. This study aimed to explore the roles and mechanism of SRY-Box Transcription Factor 2 (SOX2) on proliferation and osteogenic differentiation of MC3T3-E1 cells. Bone morphogenetic protein 2 (BMP2) was used to induce the osteogenic differentiation of MC3T3-E1 cells. The expression of SOX2 was determined by quantitative real-time PCR (RT-PCR) at different time points after induction. The SOX2 overexpression plasmids were constructed and transfected into MC3T3-E1 cells. Osteogenic differentiation was evaluated by Alizarin Red S staining and alkaline phosphatase (ALP) assay. The expressions of osteogenic differentiation markers including runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteocalcin (OCN) were detected by western blot assay. Luciferase reporter and CHIP assays were used to confirm that SOX2 regulated the transcriptional activation of leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4). We found that SOX2 was down-regulated upon BMP2-induced osteogenic differentiation in MC3T3-E1 cells. Overexpression of SOX2 effectively inhibited osteogenic differentiation with decreased ALP activity, calcification, and osteogenic differentiation markers' expression including Runx2, OPN, and OCN. LGR4 was identified as a target of SOX2, and the inhibitory effect of SOX2 on osteogenic differentiation was reversed by knockdown of LGR4. The present study confirmed that SOX2 suppressed osteogenic differentiation of MC3T3-E1 cells through targeting LGR4, which possesses a therapeutic strategy for bone formation and generation.

[Threading lasso fixation versus full-thickness conversion in repairing articular-sided partial-thickness supraspinatus tendon tears].

OBJECTIVE: To compare the effect of two different arthroscopic procedures, threading lasso fixation and full-thickness conversion, for repairing articular-sided partial-thickness supraspinatus tendon tear. METHODS: From July 2015 to November 2018, 21 patients with articular-sided partial-thickness supraspinatus tendon tears underwent arthroscopic modified threading lasso fixation repair(group A). There were 12 males and 9 females in the group, with an average age of(53.2±6.4)years old. Twenty-four patients with articular-sided partial-thickness supraspinatus tendon tears received arthroscopic full-thickness conversion repair(group B). In this group, there were 14 males and 10 females, with an average age of (55.7±5.2) years old. The American Shoulder and Elbow Surgeons (ASES) score and University of California Los Angeles (UCLA) shoulder score were used to evaluate preoperative and postoperative clinical function. MRI was used to examine the healing status of the reconstructed rotator cuff. RESULTS: All patients were followed up, and the duration ranged from 20 to 27 months, with a mean of (23.7±3.1) months. In threading lasso fixation group, ASES score and UCLA score increased from 50.6±6.4 and 15.6±2.7 preoperatively to 87.3±5.2 and 31.6±2.4 postoperatively. In full-thickness conversion group, ASES score and UCLA score increased from 52.3±5.6 and 16.8±2.4 scores to 90.1±4.8 and 32.1±2.8. There were also no significant differences in ASES score and Constant score between the two groups before and after operation. There were no significant differences in rotator cuff healing between the two groups(χ2=2.374, P=0.128). CONCLUSION: For the treatment of articular-sided partial-thickness supraspinatus tendon tears both arthroscopic repairs employing threading lasso fixation and full-thickness conversion could achieve satisfactory clinical results, and there are no significant differences in clinical outcomes between the two techniques. Arthroscopic repair with threading lasso fixation is a novel transtendinous procedure in which integrity of the tendon can be preserved.

Erratum: N-myc Downstream-Regulated Gene 2 (NDRG2) Promotes Bone Morphogenetic Protein 2 (BMP2)-Induced Osteoblastic Differentiation and Calcification by Janus Kinase 3 (JAK3)/Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway.

The authors have found that a picture in Figure 6C is needed to be corrected. Reference: SunYu Chen, JianKun Wang, Chao Cai, Xiaoyan Xie. N-myc Downstream-Regulated Gene 2 (NDRG2) Promotes Bone Morphogenetic Protein 2 (BMP2)-Induced Osteoblastic Differentiation and Calcification by Janus Kinase 3 (JAK3)/Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway. Med Sci Monit 2020; 26:e918541. DOI: 10.12659/MSM.918541.

Efficacy of threading lasso fixation in repairing partial articular supraspinatus tendon avulsion lesions: a retrospective study.

BACKGROUND: The partial articular supraspinatus tendon avulsion (PASTA) lesion repair remains a topic of debate. We have performed in situ repair of PASTA lesions using a potentially viable threading lasso fixation technique. This retrospective case series aimed to evaluate the clinical outcomes of PASTA lesion repair using threading lasso fixation. To the best of our knowledge, this is the first study to review this technique and its outcomes in terms of pain and upper extremity function. METHODS: Twenty-five patients with PASTA lesions who were treated with threading lasso fixation were reviewed. All patients were followed up for at least 1 year. Preoperative and follow-up data were retrospectively collected and reviewed. Clinical outcomes were assessed to evaluate the efficacy of the surgery. RESULTS: There were no postoperative complications. The average follow-up period was 25.7 (22-27) months. At the last follow-up, all patients underwent follow-up magnetic resonance imaging; only two cases showed a partially healed tendon and no case converted to full-thickness tear. Furthermore, shoulder pain decreased and mobility was recovered, with statistically significant differences in all scoring measures. Specifically, the mean visual analog scale score decreased from 5.4 ± 1.2 before surgery to 1.1 ± 0.8 at the last follow-up (t = 14.908, P < 0.01), and the mean American Shoulder and Elbow Surgeons Shoulder Assessment Form score improved significantly from 51.6 ± 6.4 to 89.3 ± 5.2 (t = 22.859, P < 0.01). Additionally, the mean University of California Los Angeles score improved from 17.8 ± 3.5 preoperatively to 32.3 ± 1.4 (t = 19.233, P < 0.01). CONCLUSIONS: Arthroscopic repair using threading lasso fixation is a novel transtendinous technique for patients with partial articular supraspinatus tendon avulsion. Tendon integrity is preserved with this method, which may result in improved function. Overall, threading lasso fixation technique is an effective treatment.

Autophagy promotion enhances the protective effect of Morroniside on human OA chondrocyte.

Morroniside plays a therapeutic role in knee osteoarthritis (OA) by protecting chondrocytes. PI3K/AKT signaling is involved in the regulation of chondrocytes by Morroniside. PI3K/AKT suppresses autophagy through downstream signaling. However, the regulation of chondrocyte autophagy by Morroniside and the significance of the above effect on protecting chondrocytes aren't clear. The results showed that Morroniside inhibited the autophagiy of human OA chondrocytes. Besides, both PI3K inhibitors and mTOR inhibitors significantly reversed the autophagy reduced by Morroniside, but had no effect on the protective effect of Morroniside on chondrocytes. However, the enhanced autophagy caused by overexpression of autophagic genes enhanced the protective effect of Morroniside on chondrocytes. In conclusion, Morroniside represses the autophagy of human OA chondrocyte, which is related to PI3K/mTOR pathway. Moreover, the upregulation of autophagy further promoted the role of Morroniside in treating chondrocytes. Our data present a potential clue for the therapeutic strategies of Morroniside in treating OA.

N-myc Downstream-Regulated Gene 2 (NDRG2) Promotes Bone Morphogenetic Protein 2 (BMP2)-Induced Osteoblastic Differentiation and Calcification by Janus Kinase 3 (JAK3)/Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway.

BACKGROUND Osteoporosis is an osteolytic disease resulted from imbalance in bone homeostasis. Studies indicated that N-myc downstream-regulated gene 2 (NDRG2) could affect the osteoclast differentiation. However, the effect of NDRG2 on osteoblastic differentiation and calcification remains unknown. Hence, we aimed to analyze the effect of NDRG2 on the proliferation and differentiation of osteoblasts. MATERIAL AND METHODS The differentiation of bone morphogenetic protein 2 (BMP2) induced MC3T3-E1 cells was observed by the microscope. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis detected the expression of BMP2, NDRG2, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), osterix (OSX), and osteocalcin (OCN). Alkaline phosphatase (ALP) activity assay was detecting the ALP activity and alizarin red staining assay was analyzing intracellular calcium salt deposition. The cell transfection was also verified by RT-qPCR analysis. RESULTS The results demonstrated that BMP2 promoted the osteoblastic differentiation with the increasing expression of Runx2, OPG, OSX, and OCN. NDRG2 expression was upregulated during osteogenic differentiation. NDRG2 overexpression promoted the expression of Runx2, OPG, OSX, and OCN, and increased the ALP activity while NDRG2 inhibition reversed the changes. NDRG2 overexpression increased the intracellular calcium salt deposition and NDRG2 inhibition reversed the changes. The role of NDRG2 in osteoblastic differentiation and calcification was played through the JAK3/STAT3 signal pathway. CONCLUSIONS The presented data indicated that NDRG2 promoted BMP2-induced osteoblastic differentiation and calcification by activating the JAK3/STAT3 signal pathway.