Intervertebral disc degeneration (IDD) is characterized by oxidative-stress driven progressive apoptosis and senescence of nucleus pulposus mesenchymal stem cells (NP-MSCs). MOTS-c, a 16-amino acid peptide encoded by the mitochondrial 12S rRNA open reading frame, has emerged as a key regulator of cellular metabolism, oxidative stress, and senescence. This study investigated the therapeutic potential of MOTS-c in countering tert-butyl hydroperoxide (TBHP)-induced oxidative damage in NP-MSCs, and we developed a novel biomaterial strategy for IDD treatment.Key findings include.
MOTS-c significantly attenuated TBHP-induced NP-MSC apoptosis (Annexin V+/PI + cells reduced by 48 %, p < 0.001), senescence (SA-β-gal + cells decreased by 52 %, p < 0.005), and ROS overproduction (35 % reduction, p < 0.0001) via activation of the AMPK/SIRT1 pathway. Pharmacological inhibition of SIRT1 abolished these protective effects, confirming pathway specificity.
A sustained-release MOTS-c delivery system (RAD/RMOTS-c) was engineered by conjugating MOTS-c to the self-assembling RADA16-I peptide. The hydrogel exhibited a β-sheet-rich nanofibrous structure (fiber diameter: 362.6 nm), shear-thinning rheology (viscosity: 131-217 Pa s), and sustained peptide release over 7 days.
RAD/RMOTS-c enhanced NP-MSC viability (1.8-fold vs. control, p < 0.005) and extracellular matrix (ECM) synthesis, elevating collagen II/aggrecan expression (2.3-fold, p < 0.05) while suppressing collagen I (63 % reduction, p < 0.001).In Vivo Therapeutic Validation: In a rat IDD model, RAD/RMOTS-c injection preserved disc height (DHI%: 82.4 vs. 58.7 in IDD group, p < 0.001), restored T2-weighted MRI signals (1.5-fold increase, p < 0.001), and reduced histological degeneration scores by 44 % compared to untreated controls (p < 0.001).
This work (1) demonstrates the association between MOTS-c's anti-degenerative effects and AMPK/SIRT1 signaling in NP-MSCs and (2) pioneers a peptide-hydrogel hybrid system that synergistically combines mitochondrial protection with structural support for disc regeneration. The findings can advance IDD therapy toward biology-driven, minimally invasive solutions, aligning with the paradigm of functional biomaterials for degenerative diseases.
© 2025 The Authors.

Cross-linked polymer blends from natural compounds, namely gelatin (Gel), chitosan (CS), and synthetic poly (vinyl alcohol) (PVA), have received increasing scrutiny because of their versatility, biocompatibility, and ease of use for tissue engineering. Previously, Gel/CS/PVA [1:1:1] hydrogel produced via the freeze-drying process presented enhanced mechanical properties. This study aimed to investigate the biocompatibility and chondrogenic potential of a steam-sterilized Gel/CS/PVA hydrogel using differentiation of human adipose-derived mesenchymal stromal cells (AD-hMSC) and cartilage marker expression. AD-hMSC displayed fibroblast-like morphology, 90% viability, and 69% proliferative potential. Mesenchymal profiles CD73 (98.3%), CD90 (98.6%), CD105 (97.0%), CD34 (1.11%), CD45 (0.27%), HLA-DR (0.24%); as well as multilineage potential, were confirmed. Chondrogenic differentiation of AD-hMSC in monolayer revealed the formation of cartilaginous nodules composed of glycosaminoglycans after 21 days. Compared to nonstimulated cells, hMSC-derived chondrocytes shifted the expression of CD49a from 2.82% to 40.6%, CD49e from 51.4% to 92.2%, CD54 from 9.66 to 37.2%, and CD151 from 45.1% to 75.8%. When cultured onto Gel/CS/PVA hydrogel during chondrogenic stimulation, AD-hMSC changed to polygonal morphology, and chondrogenic nodules increased by day 15, six days earlier than monolayer-differentiated cells. SEM analysis showed that hMSC-derived chondrocytes adhered to the surface with extended filopodia and abundant ECM formation. Chondrogenic nodules were positive for aggrecan and type II collagen, two of the most abundant components in cartilage. This study supports the biocompatibility of AD-hMSC onto steam-sterilized GE/CS/PVA hydrogels and its improved potential for chondrocyte differentiation. Hydrogel properties were not altered after steam sterilization, which is relevant for biosafety and biomedical purposes.

Programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitor is one of the most popular immune therapies. Biomarkers for predicting response are highly needed, but no biomarkers are widely used till now.
From February 2018 to April 2019, pan-cancer patients treated with PD-1 or PD-L1 inhibitor as a single agent in our center were included. The benefit group included patients with partial response, complete response and stable disease, while the patients with progressive disease were classified into the nonbenefit group, according to the RECIST 1.1 criteria. Baseline peripheral blood was sampled to determine absolute monocyte count (AMC) and/or classical monocyte frequency (CMF) of peripheral blood mononuclear cells. Then, the association of the above-mentioned two biomarkers with response or progression-free survival (PFS) was evaluated.
In total, 107 patients enrolled in the present study. The nonbenefit group had significantly larger number of AMC than benefit group (P<0.001), and patients with higher AMC had decreased PFS time (P=0.001). Of 39 patients tested for CMF, the nonbenefit group had significantly higher CMF than benefit group (P=0.002), and patients with higher CMF had significantly decreased PFS time (P=0.002). The sensitivity of AMC and CMF was 87.9% and 85.7%, respectively, and the specificity was 44.9% and 61.1%, respectively. Multivariate analysis showed high baseline CMF and AMC were both significantly associated with decreased PFS time.
Baseline CMF and baseline AMC can be potential pan-cancer biomarkers to predict efficacy of PD-1/PD-L1 inhibitors, especially in the PD-L1 subgroup.
© 2021 The Author(s).

To date, there has been no effective treatment for intervertebral disc degeneration (IDD). Nucleus pulposus-derived mesenchymal stem cells (NPMSCs) showed encouraging results in IDD treatment, but the overexpression of reactive oxygen species (ROS) impaired the endogenous repair abilities of NPMSCs. 6-gingerol (6-GIN) is an antioxidant and anti-inflammatory reagent that might protect NPMSCs from injury.
To investigate the effect of 6-GIN on NPMSCs under oxidative conditions and the potential mechanism.
The cholecystokinin-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of 6-GIN. ROS levels were measured by 2´7´-dichlorofluorescin diacetate analysis. Matrix metalloproteinase (MMP) was detected by the tetraethylbenzimidazolylcarbocyanine iodide assay. TUNEL assay and Annexin V/PI double-staining were used to determine the apoptosis rate. Additionally, autophagy-related proteins (Beclin-1, LC-3, and p62), apoptosis-associated proteins (Bcl-2, Bax, and caspase-3), and PI3K/Akt signaling pathway-related proteins (PI3K and Akt) were evaluated by Western blot analysis. Autophagosomes were detected by transmission electron microscopy in NPMSCs. LC-3 was also detected by immunofluorescence. The mRNA expression of collagen II and aggrecan was evaluated by real-time polymerase chain reaction (RT-PCR), and the changes in collagen II and MMP-13 expression were verified through an immunofluorescence assay.
6-GIN exhibited protective effects against hydrogen peroxide-induced injury in NPMSCs, decreased hydrogen peroxide-induced intracellular ROS levels, and inhibited cell apoptosis. 6-GIN could increase Bcl-2 expression and decrease Bax and caspase-3 expression. The MMP, Annexin V-FITC/PI flow cytometry and TUNEL assay results further confirmed that 6-GIN treatment significantly inhibited NPMSC apoptosis induced by hydrogen peroxide. 6-GIN treatment promoted extracellular matrix (ECM) expression by reducing the oxidative stress injury-induced increase in MMP-13 expression. 6-GIN activated autophagy by increasing the expression of autophagy-related markers (Beclin-1 and LC-3) and decreasing the expression of p62. Autophagosomes were visualized by transmission electron microscopy. Pretreatment with 3-MA and BAF further confirmed that 6-GIN-mediated stimulation of autophagy did not reduce autophagosome turnover but increased autophagic flux. The PI3K/Akt pathway was also found to be activated by 6-GIN. 6-GIN inhibited NPMSC apoptosis and ECM degeneration, in which autophagy and the PI3K/Akt pathway were involved.
6-GIN efficiently decreases ROS levels, attenuates hydrogen peroxide-induced NPMSCs apoptosis, and protects the ECM from degeneration. 6-GIN is a promising candidate for treating IDD.
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Macrophages are divided into two types: M1- and M2-type macrophages. Both types of macrophages serve important roles during the process of inflammation. M1-type macrophages release various pro-inflammatory cytokines, such as IL-1, IFN-γ and other inflammatory mediators, such as nitric oxide, glutamate and reactive oxygen species to generate inflammation. In contrast, M2-type macrophages counteract the pro-inflammatory M1 conditions and promote tissue repair by secreting anti-inflammatory cytokines, such as IL-10. In spinal cord injury (SCI), an imbalance in M1/M2 macrophages leads to irreversible tissue destruction. Thus, it is crucial to increase the number of M2-type macrophages and promote M2 polarization of macrophages in SCI. Accordingly, in this study an in vitro co-culture system was established to investigate the effect of neural stem cells (NSCs) on macrophages. The results of the present study demonstrated that NSCs induced M2 polarization and suppressed M1 polarization of macrophages in an interleukin (IL)-4-dependent manner. Furthermore, the nuclear factor (NF)-κB/p65 signaling pathway was involved in the M1 polarization of macrophages and NSCs suppressed the activation of the NF-κB/p65 pathway in an IL-4-dependent manner to induce M2 macrophage polarization. These findings provide more insight into SCI and help to identify novel treatment strategies.
Copyright © 2020, Spandidos Publications.