Dual pH/redox-responsive hyperbranched polymeric nanocarriers with TME-trigger size shrinkage and charge reversible ability for amplified chemotherapy of breast cancer.

A novel pH/redox-responsive hyperbranched MeO-PEG-b-(NIPAAm-co-PBAE) nanoparticles (NPs) were designed with size shrinkage and charge-reversible potential for targeted delivery of docetaxel (DTX) to MDA-MB-231 cell lines. In the tumor microenvironment (TME), amine protonation induces charge reversal and disulfide bond cleavage under high TME GSH concentration causing size shrinkage, improved deep tumor penetration, and active targeting of the therapeutic agents. These nano drug delivery systems (NDDSs) significantly promoted cancer cell uptake (~ 100% at 0.5 h), facilitating site-specific delivery and deep tumor penetration. The MTT assay revealed significantly higher cytotoxicity (P value < 0.0001) for DTX-loaded NPs compared to free DTX. Cell cycle analysis revealed G2/M (58.3 ± 2.1%) and S (21.5 ± 1.3%) arrest for DTX-loaded NPs, while free DTX caused G2/M (67.9 ± 1.1%) and sub-G1 (10.3 ± 0.8%) arrest. DTX-loaded NPs induced higher apoptosis (P value < 0.001) in MDA-MB-231 cells (71.5 ± 2.8%) compared to free DTX (42.3 ± 3.1%). Western blotting and RT-PCR assays confirmed significant up-regulation of protein levels and apoptotic genes by DTX-loaded NPs compared to free DTX. In conclusion, TME-responsive charge reversal and size-shrinkable smart NDDSs designed based on low pH, and high glutathione (GSH), offer more effective site-specific delivery of therapeutic agents to tumors.

Conditioned Medium Treatment for the Improvement of Functional Recovery after Spinal Cord Injury: A Meta-Analysis Study.

BACKGROUND: While there is no certain treatment for spinal cord injury (SCI), stem cellbased therapy may be an attractive alternative, but the survival and differentiation of cells in the host tissue are poor. Conditioned medium (CM) has several beneficial effects on cells. OBJECTIVE: In this meta-analysis study, we examined the effect of CM on SCI treatment. METHODS: After searching on MEDLINE, SCOPUS, EMBASE, and Web of Science, first and secondary screening were performed based on title, abstract, and full text. The data were extracted from the included studies, and meta-analysis was performed using STATA.14 software. A standardized mean difference (SMD) with a 95% confidence interval was used to report findings. Quality control and subgroup analysis were also performed. RESULTS: The results from 52 articles and 61 separate experiments showed that CM had a significantly strong effect on improving motor function after SCI (SMD = 2.58; 95% CI: 2.17 to 2.98; p < 0.001) and also analysis of data from 12 articles demonstrated that CM reduced the expression of GFAP marker (SMD = -4.16; p < 0.0001) compared to SCI group without any treatment. Subgroup analysis showed that treatment with CM of neural stem cells was better than CM of mesenchymal stem cells. It was more effective after a mild lesion than a moderate or severe one. The improvement was more pronounced with <4 weeks than >4 weeks follow-up. CONCLUSION: CM had a significant effect in improving motor function after SCI, especially in cases of mild lesions. It has been observed that if CM originates from the neural stem cells, it has a more significant effect than mesenchymal cells.

Evaluation of epigenetic (HDAC, DNMT) and pain (Gad65, TGF) factors following photobiomodulation therapy in a neuropathic pain model.

Photobiomodulation therapy (PBMT) is converted to the most common analgesic treatment before the whole mechanism is yet to be discovered. This study for the first time was designed to investigate alternations of epigenetic factors after pain and PBMT. The CCI model was chosen to induce pain. Pain evaluation tests including plantar, acetone, von Frey, and pinch were done weekly. Then spinal cord tissue was isolated for evaluating mRNA expression of DNMT3a, HDAC1, and NRSF using RT-qPCR method, and protein expression factors of HDAC2 and DNMT3a using western blotting. GAD65 and TGF-ß proteins were assessed by the IHC method. PBMT increased the pain threshold up to the point where it roughly met the pain threshold of the control group. After three weeks of treatment, both PBMT protocols demonstrated a reduction in allodynia and hyperalgesia. While some molecules, such as TGF-ß and Gad65, increased following PBMT, we observed no inhibition of NRSF, HDAC1, and DNMT3a expression despite implementing two different protocols.

Effects of Electrospun Nanofibers on Motor Function Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Nanofibers made by electrospinning have been used as bridging materials in animal models to regenerate nerves after spinal cord injury (SCI). In this meta-analysis study, we investigated the effect of these nanofibers on the motor function of animals after SCI. An extensive search in databases was performed. After primary and secondary screening, data included functional behavior, expression of glial fibrillary acidic protein, neurofilament-200 (NF-200), and ß-tubulin III were taken from the articles. The quality control of the articles, statistical analysis, and subgroup analysis were performed. The results from 14 articles and 16 separate experiments showed that electrospun nanofibers used alone could improve motor behavior and reduce glial injury after SCI.

Dietary fiber intake and all-cause and cause-specific mortality: An updated systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Accumulating evidence supports the effects of dietary fiber on the risk of non-communicable diseases (NCDs). However, there is no updated systematic review and meta-analysis that compares and pools the effect of different types of fiber on mortality. METHODS: In this systematic review and meta-analysis, all prospective cohort studies that evaluated the relationship between dietary fiber intake and all-cause or cause-specific mortality were included. The PubMed, SCOPUS, and Web of Science databases were searched up to October 2022. Data extraction and quality assessment were performed by two researchers independently. Heterogeneity between studies was assessed using Chi-square based test. Random/fixed effect meta-analysis was used to pool the hazard ratios (HR) or relative risks (RR) and 95 % confidence intervals (CI) for the association between different types of fiber and mortality. RESULTS: This systematic review included 64 eligible studies, with a total sample size of 3512828 subjects, that investigated the association between dietary fiber intake and mortality from all-cause, cardiovascular disease (CVD), and cancer. Random-effect meta-analysis shows that higher consumption of total dietary fiber, significantly decreased the risk of all-cause mortality, CVD-related mortality, and cancer-related mortality by 23, 26 and 22 % (HR:0.77; 95%CI (0.73,0.82), HR:0.74; 95%CI (0.71,0.77) and HR:0.78; 95%CI (0.68,0.87)), respectively. The consumption of insoluble fiber tended to be more effective than soluble fiber intake in reducing the risk of total mortality and mortality due to CVD and cancer. Additionally, dietary fiber from whole grains, cereals, and vegetables was associated with a reduced risk of all-cause mortality, while dietary fiber from nuts and seeds reduced the risk of CVD-related death by 43 % (HR:0.57; 95 % CI (0.38,0.77)). CONCLUSION: This comprehensive meta-analysis provides additional evidence supporting the protective association between fiber intake and all-cause and cause-specific mortality rates.

pH/redox responsive size-switchable intelligent nanovehicle for tumor microenvironment targeted DOX release.

Tumor microenvironment (TME) targeted strategy could control the drug release in tumor cells more accurately and creates a new opportunity for enhanced site-specific targeted delivery. In this study, (PAA-b-PCL-S-S-PCL-b-PAA) copolymeric nanoparticles (NPs) with size-switchable ability and dual pH/redox-triggered drug release behavior were designed to significantly promote cancer uptake (cell internalization of around 100% at 30 min) and site-specific targeted doxorubicin (DOX) delivery in MDA-MB-231 tumor cells. NPs surface charge was shifted from - 17.8 to - 2.4 and their size shrunk from 170.3 to 93 nm in TME. The cell cycle results showed that DOX-loaded NPs showed G2/M (68%) arrest, while free DOX showed sub-G1 arrest (22%). Apoptosis tests confirmed that the cells treated with DOX-loaded NPs showed a higher amount of apoptosis (71.6%) than the free DOX (49.8%). Western blot and RT-PCR assays revealed that the apoptotic genes and protein levels were significantly upregulated using the DOX-loaded NPs vs. the free DOX (Pvalue < 0.001). In conclusion, dual pH/redox-responsive and size-switchable DOX-loaded NPs developed here showed outstanding anti-tumoral features compared with free DOX that might present a prospective platform for tumor site-specific accumulation and drug release that suggest further in vivo research.

The promising impact of Bemcentinib and Repotrectinib on sleep impairment in Alzheimer's disease.

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, demands effective medication to alleviate symptoms. This study focused on sleep impairment as an overt clinical symptom and tauopathy as a prominent molecular symptom of this disease. Multiple compounds from three biomolecule libraries (719 compounds; ChemDiv:366 - ChEMBL:180 - PubChem:173) were evaluated for potential binding affinity and safety using AutoDock Vina and pkCSM, respectively, resulting in the selection of four candidate compounds (Lestaurtinib, Repotrectinib, Bemcentinib, and Zotiraciclib). Due to the similarity of Repotrectinib and Bemcentinib binding sites to ATP, 300 ns Martini 3 coarse-grained molecular dynamics (MD) was performed on these two molecules and ATP by NAMD. The stability of tau protein in the presence of drugs was assessed using a 200 ns Martini 3 MD simulation. Binding site analysis discloses Bemcentinib and Repotrectinib as two inhibitors occupying most amino acids in binding with ATP. The RMSD and RMS average correlation results revealed protein containing Bemcentinib and Repotrectinib to have a more stable state compared to ATP in the first 220 ns simulation. There was only a single detachment of Bemcentinib, while Repotrictinib detached twice at the end of the simulation. Eventually, adding Bemcentinib and Repotrectinib to the enzyme-tau complex significantly increased the number of tau detachments during the 200 ns simulation. We report Bemcentinib and Repotrectinib, formerly prescribed for cancer, as potential inhibitors of the CK1 δ. Besides their high binding affinity compared to ATP, they can inhibit all ATP-binding sites and alter the tau binding stability.Communicated by Ramaswamy H. Sarma.

Evaluation of photobiomodulation therapy (117 and 90s) on pain, regeneration, and epigenetic factors (HDAC 2, DNMT3a) expression following spinal cord injury in a rat model.

BACKGROUND: Photobiomodulation therapy (PBMT), due to its anti-inflammatory, analgesic effects, and most importantly as a non-invasive procedure, has currently gained a special setting in pain relief and the treatment of Spinal cord injuries (SCI). However, the mechanism of action of the PBM is not yet completely understood. METHODS: In this study, SCI is induced by an aneurysm clip, and PBM therapy was applied by a continuous-wave (CW) laser with a wavelength of 660 nm. Adult male rats were divided into four groups: Control, SCI, SCI + PBMT 90s, and SCI + PBMT 117s. After 7 weeks, hyperalgesia, allodynia, and functional recovery were assessed. Fibroblasts infiltrating the spinal cord were counted after H&E staining. The expression of epigenetic factors (HDAC2, DNMT3a), protein relevant for pain (GAD65), and astrocytes marker (GFAP) after 4 weeks of daily PBMT (90 and 117s) was probed by western blotting. RESULTS: Both PBMTs (90 and 117s) significantly improved the pain and ability to move and fibroblast invasion was reduced. SCI + PBMT 90s, increased GAD65, HDAC2, and DNMT3a expression. However, PBMT 117s decreased GFAP, HDAC2, and DNMT3a. CONCLUSION: PBMT 90 and 117s improved the pain, and functional recovery equally. The regulation of epigenetic mechanisms appears to be a significant effect of PBMT117s, which emphasizes on impact of radiation duration and accumulative energy.

Could conditioned medium be used instead of stem cell transplantation to repair spinal cord injury in animal models? Identifying knowledge gaps.

The drawbacks of stem cell (SC) therapies have led to investigations of SC conditioned medium (CM) instead of SC transplantation in the repair of spinal cord injury (SCI). However, the effectiveness of CM in comparison with cell transplantation in SCI models remain an open and intriguing question. The focus of this review was to survey existing publications addressing this comparison. The review included articles from electronic databases Medline, Embase, Scopus, and Web of Science that included comparisons of the effects of CM versus SC transplantation and versus controls on locomotion after SCI. The search yielded 5 studies and 6 experiments. The results indicated that there was insufficient evidence to conclude that treatment with CM and source cells were equally effective (SMD = 0.12; 95% CI = -0.36 to 0.59; p = 0.07). Regarding investigations of separate effects of SCs versus CM, there currently is limited evidence on efficacy in SCI models. This highlights a notable concern affecting this field. Thus, we identified critical knowledge gaps concerning comparisons of the efficacy of therapeutic application of SC and their derived CM on functional recovery following SCI.

Time-dependent photobiomodulation management of neuropathic pain induced by spinal cord injury in male rats.

Neuropathic pain (NP) following spinal cord injury (SCI) often lasts for a long time and causes a range of problems that reduce the quality of life. Current treatments are not generally effective; however, photobiomodulation therapy (PBMT) has made some progress in this area. Due to the novelty of this treatment, standard therapeutic protocols have not yet been agreed upon. In the present study, we compare the analgesic effect of two PBMT protocols (2 and 4 weeks of radiation). A total of thirty-two adult male Wistar rats were divided into four groups: control, SCI, 2 W PBMT, and 4 W PBMT. SCI was induced by an aneurism clip and PBMT used a 660-nm, initiated 30 min post-SCI, and continued daily for 2 or 4 weeks. Functional recovery, hyperalgesia, and allodynia were measured weekly. At the end of the study, the Gad65, interleukin 1-alpha (IL1α), interleukin 10 (IL10), IL4, and purinergic receptor (P2xR and P2yR) expressions were measured. Data were analyzed by Prism6. The results showed PBM irradiation for 2 and 4 weeks had the same effects in improving hyperalgesia. In the case of allodynia and functional recovery, 4 W PBMT was more effective (p<0.01). 4 W PBMT increased the Gad65 expression (p <0.001) and reduced P2Y4R (p <0.05) compared to SCI animals. The effects of 2 and 4 W PBMT were the same for IL1α, IL10, and P2X3 receptors. 4 W PBMT was more effective in reducing the complications of SCI such as pain and disability. PBMT therapy is an effective method aimed at immune system function modulation to reduce NP and motor dysfunction.

Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

Since the CNS is unable to repair itself via neuronal regeneration in adult mammals, alternative therapies need to be found. The use of cerium oxide nanoparticles to repair nerve damage could be a promising approach for spinal cord reconstruction. In this study, we constructed a scaffold containing cerium oxide nanoparticles (Scaffold-CeO2) and investigated the rate of nerve cell regeneration in a rat model of spinal cord injury. The scaffold of gelatin and polycaprolactone was synthesized, and a gelatin solution containing cerium oxide nanoparticles was attached to the scaffold. For the animal study, 40 male Wistar rats were randomly divided into 4 groups (n = 10): (a) Control; (b) Spinal cord injury (SCI); (c) Scaffold (SCI + scaffold without CeO2 nanoparticles); (d) Scaffold-CeO2 (SCI + scaffold containing CeO2 nanoparticles). After creation of a hemisection SCI, scaffolds were placed at the site of injury in groups c and d, and after 7 weeks the rats were subjected to behavioral tests and then sacrificed for preparation of the spinal cord tissue to measure the expression of G-CSF, Tau and Mag proteins by Western blotting and Iba-1 protein by immunohistochemistry. The result of behavioral tests confirmed motor improvement and pain reduction in the Scaffold-CeO2 group compared to the SCI group. Decreased expression of Iba-1 and higher expression of Tau and Mag in the Scaffold-CeO2 group compared to the SCI group could be the result of nerve regeneration caused by the scaffold containing CeONPs as well as relief of pain symptoms.

The Role of Intraspinal Administration of Self-Assembled Peptide on Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis Study.

BACKGROUND: Spinal cord injury (SCI) treatment is still a challenge and new treatments that help these patients are being considered. Recent studies showed that the use of self-assembled peptide (SAP) can be useful in SCI treatment. MATERIALS AND METHODS: In this meta-analysis, we investigated the effect of SAP administration on locomotion recovery after SCI. Records were obtained from a comprehensive search of data bases. Articles were scrutinized for inclusion and exclusion criteria. Data were analyzed and results were reported as standardized mean difference (SMD) with 95% CI. Subgroup analysis was also performed. RESULTS: A total of 14 studies and 17 separate experiments were included in the final analysis. Treatment with SAP structures after SCI resulted in a significant improvement in animal motor function (SMD = 1.13; 95% CI: 0.68-1.58; p < 0.0001). SAP treatment facilitated axon sprouting (SMD = 0.76; 95% CI: 0.33-1.18; p < 0.0001) and reduction of glial scar (SMD = -1.02; 95% CI: -1.94 to -0.09; p = 0.03). The difference in SAP type, its concentration, follow-up time, and SCI model had no effect on SAP effectiveness. In addition, SAP administration had a similar effect on improving locomotion in all three immediate, acute, and subacute phases which gives the good news of using this treatment for patients who are in the chronic phase. CONCLUSION: SAP treatment can be considered as a potential treatment to help the motor recovery of SCI and axon regeneration.

The potential of curcumin for treating spinal cord injury: a meta-analysis study.

INTRODUCTION: In this paper, we conducted a meta-analysis on the curcumin effect on functional recovery provided by the Basso, Beattie, Brenham (BBB) test for rats, and the Basso mouse scale (BMS) for mice after spinal cord injury (SCI) in animal models. METHOD: Data mining was performed, and the standard mean difference (SMD) between the treated and control (untreated) groups was calculated using the STATA software. Quality control and subgroup analysis were performed. RESULTS: The analysis includes 24 experimental studies that showed curcumin had a strong significance in improving functional recovery after SCI (SMD = 3.38; 95% CI: 2.54-4.22; p < 0.001). When curcumin was administered daily, it had a stronger effect than single-dose treatment or weekly administration. Despite the same effect in the follow-up time before and after 4 weeks post-injury, but later 9 weeks, curcumin had only a moderate effect. Curcumin also significantly reduced the expression of GFAP (Glial fibrillary acidic protein) marker compared to untreated groups. CONCLUSION: These findings suggest that daily administration of curcumin can be an effective approach to improving functional recovery after SCI.

Combined Parental Thrombophilia Gene Mutation Defects in Couples with Repeated Pregnancy Loss.

Background: Several genetic mutations in female thrombotic defects have recently been shown to affect recurrent pregnancy loss (RPL); however, it is unclear which common parental mutations are involved in thrombosis-associated repeated pregnancy loss RPL. Aims: In this study, the prevalence of some combined parental thrombophilia gene mutation defects was studied in couples with RPL. Settings and Design: The observational study was done in babol infertility research center (Iran) in 2022. Materials and Methods: Sixty-two infertile women with a history of RPL and their male partners (124 individuals) participated in this study. The frequencies of common defects associated with methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, factor V Leiden, protein C, protein S and homocysteine were analysed in these couples. Statistical analysis used: The data were statistically analysed using the Mann-Whitney test. Results: Sixty-two couples (124 individuals) were analysed. 56.2% of couples with a history of RPL had MTHFR C677T and 23.1% had MTHFR A1298C. Forty percent of couples showed homocysteine deficiency and 12.5% protein C deficiency. Other genes tested were only observed in the mother or father but not both. Conclusions: Results obtained with RPL couples demonstrate the importance of further investigating combined parental thrombophilia gene mutation defects (not only maternal).

Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis.

OBJECTIVE: About 30% of all nanoparticle products contain silver nanoparticles (AgNPs). With the increasing use of AgNPs in industry and medicine, concerns about the adverse effects on the environment, and the possible toxicity of these particles to primary cells and towards organs such as the brain and nervous system increased. In this paper, the toxicity of AgNPs in neurons and brain of animal models was investigated by a systematic review and meta-analysis. METHODS: The full texts of 26 relevant studies were reviewed and analyzed. Data from nine separate experiments in five articles were analyzed by calculating the standardized mean differences between viability of treated animals and untreated groups. Subgroup analysis was conducted. In addition, a systematic review provided a complete, exhaustive summary of all articles. RESULTS: The results of the meta-analysis showed that AgNPs are able to cause neuronal death after entering the brain (standardized mean difference (SMD) = 2.87; 95% confidence interval (CI) 2.1-3.61; p < 0.001). AgNPs sized smaller or larger than 10 nm could both cause neuronal cell death. This effect could be observed for a long time (up to 6 months). Neurons from embryonic animals whose mothers had been exposed to AgNPs during pregnancy were affected as much as animals that were themselves exposed to AgNPs. Toxic effects of AgNPs on memory and cognitive function were also observed. Studies have shown that inflammation and increased oxidative stress followed by apoptosis are likely to be the main mechanisms of AgNPs toxicity. CONCLUSION: AgNPs can enter the brain with a long half-life and it can cause neuronal death after entering the brain. AgNPs can manifest proinflammatory cascades in the CNS and BBB. Some toxic effects were detected in the cerebral cortex, hypothalamus, hippocampus and others. Studies have shown that inflammation and increased oxidative stress lead to apoptosis, the main mechanism of AgNPs neurotoxicity, which can be caused by an increase in silver ions from AgNPs.

Sustained delivery of chABC improves functional recovery after a spine injury.

INTRODUCTION: Chondroitinase ABC (chABC) is an enzyme could improve regeneration and thereby improving functional recovery of spinal cord injury (SCI) in rodent models. Degradation of the active enzyme and diffusion away from the lesion are the causes of using hydrogels as a scaffold to deliver the chABC into the lesion site. In this meta-analysis, we investigated the effects of chABC embedded in a scaffold or hydrogel on the functional recovery after SCI. METHOD: Databases were searched based on keywords related to chABC and spinal cord injury (SCI). Primary and secondary screening was performed to narrow down study objectives and inclusion criteria, and finally the data were included in the meta-analysis. The standard mean difference of the score of the functional recovery that measured by Basso, Beattie, Bresnahan (BBB) test after SCI was used to analyze the results of the reported studies. Subgroup analysis was performed based on SCI model, severity of SCI, transplantation type, and the follow-up time. Quality control of articles was also specified. RESULTS: The results showed that embedding chABC within the scaffold increased significantly the efficiency of functional recovery after SCI in animal models (SMD = 1.95; 95% CI 0.71-3.2; p = 0.002) in 9 studies. SCI model, severity of SCI, injury location, transplantation type, and the follow-up time did not affect the overall results and in all cases scaffold effect could not be ignored. However, due to the small number of studies, this result is not conclusive and more studies are needed. CONCLUSION: The results could pave the way for the use of chABC embedded in the scaffold for the treatment of SCI and show that this method of administration is superior to chABC injection alone.

ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury is caused by a chain of events such as endothelial dysfunction. This study was conducted to investigate protective effects of ELABELA against myocardial I/R in Wistar rats and clarify its possible mechanisms. METHODS AND RESULTS: MI model was established based on the left anterior descending coronary artery ligation for 30 min. Then, 5 µg/kg of ELA peptide was intraperitoneally infused in rats once per day for 4 days. Western blot assay was used to assay the expression of t-ERK1/2, and p-ERK1/2 in different groups. The amount of myocardial capillary density, the expression levels of VEGF and HIF-1α were evaluated using immunohistochemistry assay. Masson's trichrome staining was utilized to assay cardiac interstitial fibrosis. The results showed that establishment of MI significantly enhanced cardiac interstitial fibrosis and changed p-ERK1/2/ t-ERK1/2 ratio. Likewise, ELA post-treatment markedly increased myocardial capillary density, the expression of several angiogenic factors (VEGF-A, HIF-1α), and reduced cardiac interstitial fibrosis by activation of ERK1/2 signaling pathways. CONCLUSION: Collectively, ELA peptide has ability to reduce myocardial I/R injury by promoting angiogenesis and reducing cardiac interstitial fibrosis through activating ERK/HIF-1α/VEGF pathway.

Prevalence of Posttraumatic Stress Disorder Symptoms Following Traumatic Spinal Cord Injury: A Systematic Review and Meta-analysis.

BACKGROUND: Limited evidence is currently available on the prevalence of posttraumatic stress disorder (PTSD) following traumatic spinal cord injury (SCI). This systematic review and meta-analysis aims to assess the prevalence and geographic distribution of PTSD symptoms after SCI. METHODS: After a search in the MEDLINE, Embase, Scopus, and Web of Science databases, two reviewers independently summarized relevant studies published through 20 October 2021. Observational studies were included. The studies were eligible if they assessed PTSD symptoms using standard self-report or clinician-based instruments. Data and results were reported using the overall prevalence and the odds ratio (OR), with 95% confidence intervals (CIs). RESULTS: 24 articles (5646 patients) met the inclusion criteria. The prevalence of PTSD symptoms ranged from 6.33% (95% CI, 2.73-13.97) to 61.76% (95% CI, 52.07-70.61). Pooled analysis demonstrated that the overall prevalence of PTSD symptoms in SCI patients was significantly higher in developing countries (41.64%; 95% CI, 31.11-52.55) than in developed countries (19.35%; 95% CI, 14.66-24.51) (OR = 1.24; 95% CI, 1.08-1.42; p = .003). The highest prevalence of PTSD symptoms was reported in South Africa (56.25%; 95% CI, 47.01-65.08), followed by Sri Lanka (45.71%; 95% CI, 30.47-61.81), and Greece (43.55%; 95% CI, 31.94-55.91). By contrast, Norway (6.33%; 95% CI, 2.73-13.97), Switzerland/Germany (8.65%; 95% CI, 4.8-13.42), and Denmark (10.71%; 95% CI, 6.89-16.30) were found to have the lowest prevalence of PTSD symptoms after SCI. CONCLUSION: Many traumatic SCI patients suffer from PTSD symptoms, and their prevalence seems to be higher in developing countries than in developed countries. These findings underscore the need to consider the psychological aspects of traumatic SCI.