Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review.

Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.

CAR T Cell Membrane Camouflaged Nanocatalyst Augments CAR T Cell Therapy Efficacy Against Solid Tumor.

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Mandibular Osteomyelitis as the Earliest Clinical Manifestation of Maxillary Sinus Lymphoma.

Extranodal natural killer/T-cell lymphoma is a distinct subtype of non-Hodgkin lymphoma that originates from natural killer cells or cytotoxic T cells. Its diagnosis is challenging due to the rarity and lack of awareness, especially in cases where osteomyelitis of the jawbone is the initial symptom. This paper reports a case of extranodal natural killer/T-cell lymphoma presenting primarily with oral ulcers. Through analyzing the clinical and pathological characteristics, differential diagnosis, treatment and prognosis, and reasons for misdiagnosis of the disease, this study aims to provide references for clinical diagnosis and treatment.

Triterpenoids from the leaves of Eleutherococcus sessiliflorus, and their antiproliferative activities in TNF-α induced HFLS-RA cells.

Five undescribed elesesterpenes L-U, along with nine known 3,4-seco-lupane-type triterpenoids were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Elesesterpene L-S, and U were lupane-type triterpenoids, whereas elesesterpene T was an oleanane-type triterpenoid, probably artifact, as suggested by LC-MS analysis. Out of the nine known compounds, five were initially identified in E. sessiliflorus. Moreover, their structures were definitively determined using spectroscopic analyses, and the absolute configurations of elesesterpenes L-M and sachunogenin 3-O-glucoside were clarified using X-ray crystallographic techniques. The absolute configuration of elesesterpene T was determined by measuring and calculating its ECD. In addition, all compounds were tested to examine their ability to inhibit the proliferation of HFLS-RA cells induced by TNF-α in vitro. Elesesterpene M, chiisanogenin, chiisanoside, and 3-methylisochiisanoside significantly inhibited HFLS-RA proliferation.

A case report of the treatment of carotid artery stenosis by staged angioplasty based on intraoperative TCD monitoring.

Objective: Cerebral hyperperfusion syndrome (CHS) is the most severe complication of carotid artery stenting (CAS) or endarterectomy (CEA). Staging treatment can effectively reduce the risk of CHS without increasing the risk of ischemic stroke. The first stage of balloon dilatation is critical for staged treatment. However, the successful criterion of the first stage balloon dilatation is still inconsistent. Method: In the current study presents a case of a 61-year-old male with bilateral internal carotid subtotal occlusion, transcranial doppler (TCD) was used to measure middle cerebral artery (MCA) flow rate on the narrow side of surgery and the results are promising. Result: Intraoperative TCD monitoring is expected to be an evaluation criterion for staged angioplasty for carotid artery stenosis. Conclusion: The approach of blood flow velocity in the brain based on intraoperative measurement of TCD during the treatment of this patient is a new idea for staging treatment in the future.

Characterisation of aroma compounds, sensory characteristics, and bioactive components of a new type of huangjiu fermented with Chinese wild rice (Zizania latifolia).

Chinese wild rice (CWR) is a nutritious and healthy whole grain, worth developing. To develop and use its value, a new type of huangjiu was brewed with CWR, and the flavour characteristics, sensory quality, functional and bioactive components were evaluated. CWR (67 flavour substances) and glutinous rice (GR)-CWR huangjiu (62 flavour substances) had a better flavour than GR huangjiu (54 flavour substances), and the overall style of GR-CWR huangjiu was more skewed towards GR. The fruity, honey, caramel-like, herb and smoky aroma attributes of CWR huangjiu were higher than those of GR huangjiu (P < 0.05), while only the alcoholic was weaker (P < 0.05) due to the lower alcohol content. The huangjiu brewed using CWR had a better taste than that brewed using only GR. Furthermore, CWR huangjiu had the highest content of total dietary fiber (732.0 ± 15.2 mg/100 g), followed by GR-CWR (307.0 ± 8.5 mg/100 g), and GR (127.0 ± 2.3 mg/100 g). CWR huangjiu also had the highest total phenolic compounds (3.32 ± 0.05 mg/100 g/%vol) and total saponins (2.46 ± 0.03 mg/100 g/%vol) contents, followed by GR-CWR and GR. This study provides guidance for exploring further possibilities for CWR in the future.

The prognostic value of co-expression of stemness markers CD44 and CD133 in endometrial cancer.

Objective: The purpose of this study was to investigate the correlation between stemness markers (CD44 and CD133) and clinical pathological features, and to further explore the prognostic value of co-expression of CD44 & CD133 in endometrial cancer (EC). Methods: Clinical data of stage I-III EC patients who underwent initial surgical treatment at two large tertiary medical centers from 2015 to 2020 were retrospectively collected. Cohen's kappa coefficient was used to show the consistency of the expression between CD44 and CD133. The correlation between co-expression of CD44 & CD133 and prognosis of EC patients was explored using univariate and multivariate Cox regression analysis. Then, the prognosis models for early-stage (stage I-II) EC patients were constructed. Finally, stratified analysis was performed for EC patients in high-intermediate-risk and high-risk groups, Kaplan-Meier analysis was used to compare the survival differences between patients with and without adjuvant therapy in different co-expression states (low expression, mixed expression, high expression) of CD44 & CD133. Results: A total of 1168 EC patients were included in this study. The consistency of the expression between CD44 and CD133 was 70.5%, the kappa coefficient was 0.384. High expression of CD44 & CD133 was associated with early FIGO stage (P=0.017), superficial myometrial invasion (P=0.017), and negative lymphatic vessel space invasion (P=0.017). Cox regression analysis showed that the co-expression of CD44 & CD133 was significantly correlated with the prognosis of early-stage (stage I-II) patients (P=0.001 for recurrence and P=0.005 for death). Based on this, the nomogram models were successfully constructed to predict the prognosis of early-stage EC patients. Meanwhile, Kaplan-Meier analysis showed that patients with adjuvant therapy had a better overall prognosis than those without adjuvant therapy in high-intermediate-risk and high-risk groups. However, there was no statistically significant difference in survival between patients with and without adjuvant therapy in high expression of CD44 & CD133 group (P=0.681 for recurrence, P=0.621 for death). Conclusion: High expression of CD44 & CD133 was closely related to the adverse prognosis of early-stage EC patients. Meanwhile, patients with high expression of CD44 & CD133 may not be able to achieve significant survival benefits from adjuvant therapy.

Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots.

The application of fertilizers and soil quality are crucial for grape fruit quality. However, the molecular data linking different fertilizer (or soil conditioner [SC]) treatments with grape fruit quality is still lacking. In this study, we investigated three soil treatments, namely inorganic fertilizer (NPK, 343.5 kg/hm2 urea [N ≥ 46%]; 166.5 kg/hm2 P2O5 [P2O5 ≥ 64%]; 318 kg/hm2 K2O [K2O ≥ 50%]), organic fertilizer (Org, 9 t/hm2 [organic matter content ≥ 35%, N + P2O5 + K2O ≥ 13%]), and SC (SC, 3 t/hm2 [humic acid ≥ 38.5%; C, 56.1%; H, 3.7%; N, 1.5%; O, 38%; S, 0.6%]), on 4-year-old Cabernet Sauvignon grapevines. Compared with the NPK- and Org-treated groups, the SC significantly improved the levels of soluble solids, tannins, anthocyanins, and total phenols in the grape berries, which are important biochemical indicators that affect wine quality. Furthermore, we conducted RNA-seq analysis on the grapevine roots from each of the three treatments and used weighted gene co-expression network analysis to identify five hub genes that were associated with the biochemical indicators of the grape berries. Furthermore, we validated the expression levels of three hub genes (ERF, JP, and SF3B) and five selected genes related to anthocyanin biosynthesis (UFGT1, UFGT2, UFGT3, GST, and AT) by using quantitative reverse transcription-polymerase chain reaction. Compared to the NPK and Org treatment groups, the SC treatment resulted in a significant increase in the transcription levels of three hub genes as well as VvUFGT1, VvUFGT3, VvGST, and VvAT. These results suggest that the SC can improve grape fruit quality by altering gene transcription patterns in grapevine roots and further influence the biochemical indices of grape fruits, particularly anthocyanin content. This study reveals that the application of SC can serve as an important measure for enhancing vineyard SC and elevating grape quality.

An Investigation of the Anisotropic Mechanical Properties of Additive-Manufactured 316L SS with SLM.

Selective laser melting (SLM) forms specimens that often exhibit anisotropic mechanical properties. Most existing research only explains that the mechanical properties of specimens perpendicular to the build direction are superior to those parallel to the build direction. In this paper, the mechanical properties of SLM 316L SS specimens with different surfaces and different directions are compared. Finally, it was found that the mechanical properties of specimens on Face 3 are stronger than those on Face 1 and Face 2, while the mechanical properties of specimens on Face 1 and Face 2 are similar. For specimens in different directions on the same surface, the mechanical properties of Face 1 and Face 2 exhibit clear anisotropy, while the mechanical properties of Face 3 tend to be isotropic. In this paper, the EBSD technique was used to analyze the specimens. It was found that the anisotropy of the mechanical properties of Face 1 and Face 2 are attributed to the presence of texture and columnar crystals in the sample. This paper can provide accurate and reliable material performance data for the practical application of SLM 316L SS, thereby guiding the optimization of engineering design and manufacturing processes.

RVG29 Peptide-Modified Exosomes Loaded with Mir-133b Mediate the RhoA-ROCK Pathway to Improve Motor and Neurological Symptoms in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Drug delivery to the brain through the blood-brain barrier (BBB) is a significant challenge in PD treatment. Exosomes, which can efficiently traverse the BBB, which many drugs cannot penetrate, are ideal natural carriers for drug delivery. In this study, the BBB shuttle peptide was modified on the exosome surfaces. Three types of exosomes were constructed, each modified with a distinct peptide (RVG29, TAT, or Ang2) and loaded with miR-133b. The safety and brain-targeting capabilities of these peptide-modified exosomes were then evaluated. Finally, the mechanism by which RVG29-Exo-133b regulates the RhoA-ROCK signaling pathway was investigated. The findings indicate that the three peptide-modified exosomes were adequately tolerated, safe, and effectively assimilated in vivo and ex vivo, with RVG29 exhibiting superior targeting to the brain. Furthermore, RVG29-Exo-133b decreased the phosphorylation level of the Tau protein by targeting the RhoA-ROCK signaling pathway. It also enhanced the motor function in mice with PD, thereby reducing the degree of depression, improving dopaminergic neuron function, and attenuating 6-OHDA-induced nerve damage. In this study, we developed a stable drug delivery mechanism that targets the intracerebral region using exosomes. Furthermore, a novel strategy was developed to manage PD and can potentially serve as a preclinical basis for utilizing exosomes in the diagnosis and treatment of neurodegenerative conditions.

The spatial spillover effects of clean energy consumption and production on sustainable economic development in China.

The massive consumption of fossil energy has resulted in high CO2 emissions, posing a formidable challenge to global sustainable economic development (SED). As countries endeavor to shift from fossil to clean energy sources to achieve SED, research on the impact of clean energy is scarce, and quantitative analysis is lacking. This study measured China's SED and used a spatial econometric model to examine the impact of clean energy consumption and production on SED across 30 provinces in China from 2008 to 2020. Results show that (1) China's SED exhibits significant positive spatial autocorrelation characteristics, forming a "point-to-area" development pattern. (2) Clean energy consumption, production, and consumption structure all contribute to the promotion of SED in the region and have positive spatial spillover effects. (3) A considerable regional disparity exists in the spatial impact of clean energy on SED. The eastern and central regions have significant positive spatial spillover effects, whereas the western region is opposite. Notably, the estimated coefficient of the spatial Durbin model is relatively small, reflecting China's ongoing transition to clean energy and its limited role in promoting economic sustainability. Joint efforts and differentiated policies are essential to develop clean energy and sustainable economic.

Exploring the Multifaceted Landscape of Pediatric Obstructive Sleep Apnea: Insights into Prevalence, Severity, and Coexisting Conditions.

Background: Pediatric obstructive sleep apnea (OSA) is a multifaceted disorder marked by recurrent upper airway obstruction during sleep, often coexisting with various medical conditions. This study, aimed to comprehensively analyze the Multifaceted Landscape of Pediatric Insights into Prevalence, Severity, and Coexisting Conditions. With a sample of 1928 participants, our study sought to determine the prevalence, severity, and associations between OSA and diverse conditions. Methods: Conducted retrospectively from February 2019 to April 2023, the study included pediatric patients. Data were collected through electronic health records, involving clinical assessments, medical histories, and diagnostic tests to establish OSA and coexisting condition diagnoses. Relationships between sleep parameters, apnea types, and severity indices were evaluated. Results: High OSA prevalence was evident across age groups, with severity peaking between 3 to 12 years. Among the participants, coexisting conditions included allergic rhinitis (59.6%), tonsillar hypertrophy (49.7%), adenoid hypertrophy (28.4%), and obesity (15.3%). Analysis revealed intriguing relationships between different sleep parameters and apnea types. Notable associations were observed between Obstructive Apnea (OA) and Central Apnea (CA), and Mixed Apnea (MA) displayed associations with both OA and CA. Hypopnea correlated directly with the Apnea-Hypopnea Index (AHI), reflecting its role in OSA severity. Conclusion: This study provides a comprehensive understanding of the intricate dynamics between pediatric OSA and coexisting conditions. The prevalence of OSA and its coexistence with various conditions underscore the need for comprehensive evaluation and management strategies. By revealing associations between different sleep parameters and apnea types, the study emphasizes the complexity of OSA diagnosis and management. These findings hold the potential to enhance clinical approaches, ultimately leading to improved care and outcomes for affected children.

Diffuse large B-cell lymphoma with contemporary involvement of central and peripheral nervous system: A case report and literature review.

Introduction: Simultaneous involvement of the peripheral nervous system (PNS) and central nervous system (CNS) during the same period in diffuse large B-cell lymphoma (DLBCL) is rarely documented. In this particular case, the diagnosis of diffuse large B-cell lymphoma was pathologically confirmed, with invasion into the basal ganglia, diencephalon, and several peripheral nerves. The initial clinical manifestations were dyspnoea and hyperventilation. Case presentation: The patient presented to the hospital with fatigue, dyspnoea, and limb pain for over 7 months, accompanied by progressive breathlessness and unconsciousness in the last 6 days. Initial treatment with glucocorticoids for Guillain-Barre syndrome (GBS) proved ineffective in controlling the severe shortness of breath and hyperventilation, necessitating the use of ventilator-assisted ventilation. 18-Fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) showed that the basal ganglia, brainstem, and multiple peripheral nerves were thickened and metabolically active. There were atypical cells in the cerebrospinal fluid; the pathology indicated invasive B-cell lymphoma, demonstrating a propensity toward diffuse large B-cell lymphoma (DLBCL). After receiving chemotherapy, the patient regained consciousness and was successfully weaned off ventilator assistance but died of severe pneumonia. Discussion: The early clinical manifestations of DLBCL lack specificity, and multifocal DLBCL complicates the diagnostic process. When a single primary disease cannot explain multiple symptoms, the possibility of DLBCL should be considered, and nervous system invasion should be considered when nervous system symptoms are present. Once nervous system involvement occurs in DLBCL, whether the central or peripheral nervous system, it indicates a poor prognosis.

A glycolytic metabolite that drives BRCA2 haploinsufficiency.

Many types of tumor cells alter metabolic pathways to meet their energy and biosynthetic demands for proliferation or stress adaptation. In this issue of Cell, Kong et al. find that the glycolytic metabolite methylglyoxal causes cancer-associated mutant single-base substitution features by inducing BRCA2 proteolysis, leading to functional haploinsufficiency of BRCA2.

A near-infrared fluorescent probe based FRET for ratiometric sensing of H2O2 and viscosity in live cells.

Hydrogen peroxide (H2O2) and viscosity play vital roles in the cellular environment as signaling molecule and microenvironment parameter, respectively, and are associated with many physiological and pathological processes in biological systems. We developed a near-infrared fluorescent probe, CQ, which performed colorimetric and ratiometric detection of H2O2 and viscosity based on the FRET mechanism, and was capable of monitoring changes in viscosity and H2O2 levels simultaneously through two different channels. Based on the specific reaction of H2O2 with borate ester, CQ exhibited a significant ratiometric response to H2O2 with a large Stokes shift of 221 nm, a detection limit of 0.87 µM, a near-infrared emission wavelength of 671 nm, a response time of 1 h, a wide detection ranges of 0.87-800 µM and a high energy transfer efficiency of 99.9 %. CQ could also recognize viscosity by the TICT mechanism, and efficiently detect viscosity changes caused by food thickeners. More importantly, CQ could successfully detect endogenous/exogenous H2O2 and viscosity in live HeLa cells, which was expected to be a practical tool for detecting H2O2 and viscosity in live cells.

The time-dependent expression of FPR2 and ANXA1 in murine deep vein thrombosis model and its relation to thrombus age.

Thrombus age determination in fatal venous thromboembolism cases is an important task for forensic pathologists. In this study, we investigated the time-dependent expressions of formyl peptide receptor 2 (FPR2) and Annexin A1 (ANXA1) in a stasis-induced deep vein thrombosis (DVT) murine model, with the aim of obtaining useful information for thrombus age timing. A total of 75 ICR mice were randomly classified into thrombosis group and control group. In thrombosis group, a DVT model was established by ligating the inferior vena cava (IVC) of mice, and thrombosed IVCs were harvested at 1, 3, 5, 7, 10, 14, and 21 days after modeling. In control group, IVCs without thrombosis were taken as control samples. The expressions of FPR2 and ANXA1 during thrombosis were detected using immunohistochemistry and double immunofluorescence staining. Their protein and mRNA levels in the samples were determined by Western blotting and quantitative real-time PCR. The results reveal that FPR2 was predominantly expressed by intrathrombotic neutrophils and macrophages. ANXA1 expression in the thrombi was mainly distributed in neutrophils, endothelial cells of neovessels, and fibroblastic cells. After thrombosis, the expressions of FPR2 and ANXA1 were time-dependently up-regulated. The percentage of FPR2-positive cells and the level of FPR2 protein significantly elevated at 1, 3, 5 and 7 days after IVC ligation as compared to those at 10, 14 and 21 days after ligation (p < 0.05). Moreover, the mRNA level of FPR2 were significantly higher at 5 days than that at the other post-ligation intervals (p < 0.05). Besides, the levels of ANXA1 mRNA and protein peaked at 10 and 14 days after ligation, respectively. A significant increase in the mRNA level of ANXA1 was found at 10 and 14 days as compared with that at the other post-ligation intervals (p < 0.01). Our findings suggest that FPR2 and ANXA1 are promising as useful markers for age estimation of venous thrombi.

Modulating the Mesenchymal Stromal Cell Microenvironment Alters Exosome RNA Content and Ligament Healing Capacity.

Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their clinical application remains challenging due to issues such as immunocompatibility. MSC-derived exosomes are a promising off-the-shelf therapy for promoting wound healing in a cell-free manner. However, the potential to customize the content of MSC-exosomes, and understanding how such modifications influence exosome effects on tissue regeneration remain underexplored. In this study, we used an in vitro system to compare the priming of human MSCs by two inflammatory inducers TNF-α and CRX-527 (a highly potent synthetic TLR4 agonist that can be used as a vaccine adjuvant or to induce anti-tumor immunity) on exosome molecular cargo, as well as on an in vivo rat ligament injury model to validate exosome potency. Different microenvironmental stimuli used to prime MSCs in vitro affected their exosomal microRNAs and mRNAs, influencing ligament healing. Exosomes derived from untreated MSCs significantly enhance the mechanical properties of healing ligaments, in contrast to those obtained from MSCs primed with inflammation-inducers, which not only fail to provide any improvement but also potentially deteriorate the mechanical properties. Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration.

An alkali-extracted neutral heteropolysaccharide from Phellinus nigricans used as an immunopotentiator in immunosuppressed mice by activating macrophages.

A neutral heteropolysaccharide (PNANb) was isolated with alkali (0.1 M NaOH) from mycelia of Phellinus nigricans, and the structure, immunostimulating activity and some of the underlying molecular mechanisms of action of PNANb were explored in the current study. PNANb (14.95 kDa) predominantly consisted of Gal, Glc, and Man with minor Fuc. GC-MS and NMR analyses indicated that the backbone of PNANb was mainly composed of 6-α-Galp, 2,6-α-Galp with minor 3,6-ß-Glcp, which was substituted with complex side chains at C-2 of 2,6-α-Galp and C-3 of 3,6-ß-Glcp. Notably, PNANb (50 or 100 mg/kg) possessed immunoprotective effects in cyclophosphamide (Cy)-induced immunosuppressed C57BL/6 mice, which was supported by evidence including the enhancement of spleen and thymus indices, levels of serum immunoglobulins (IgG, IgM) and cytokines (IFN-γ, IL-2, IL-4, IL-10), and macrophage activity. However, the immunostimulation effects of PNANb were decreased when macrophages were depleted, underscoring the essential role of macrophages in the beneficial effects of PNANb in Cy-induced immunosuppressed mice. Further investigations in vitro indicated that PNANb activated macrophages through MAPK/NF-κB signaling pathways mediated by Toll-like receptor 4. Therefore, PNANb can serve as a prospective immunopotentiator in immunosuppression.