Engineered platelet-based immune engager for tumor post-surgery treatment.

Tumor metastasis and recurrence are principal reasons for the high mortality and poor prognosis of cancers. Inefficient engagement between T cell and tumor cell, as well as the universal existence of immune checkpoints, are important factors to the limited immunological surveillance of the immune systems to tumor cells. Herein, an immune engager based on engineered platelets with CD3 antibody modification (P-aCD3) was constructed to facilitate the contact between T cell and tumor cell via providing the anchoring sites of above two cells. Combined with the immune checkpoint blockade strategy, P-aCD3 effectively enhanced T cell mediated cytotoxicity and inhibited tumor recurrence and metastasis in mice melanoma postoperative model and breast cancer model, resulting in significantly prolonged survival of mice.

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination.

Chemoimmunotherapy is a promising strategy in tumor treatments. In this study, immunogenic dead cells were engineered by the sequential treatment of live tumor cells with ultraviolet (UV) irradiation and cryo-shocking. The dead cells could serve as a lung-targeting vehicle and tumor vaccine after differential loading of the chemo-drug 10-hydroxycamptothecin (HCPT) and immune adjuvant Quillaja saponin-21 (QS-21) via physical absorption and chemical conjugation, respectively. After intravenous administration, the dead cells could be trapped in pulmonary capillaries and could fast release HCPT to enhance the drug accumulation in local tissues. Further, the immunogenic dead cells elicited antitumor immune responses together with the conjugated adjuvant QS-21 to achieve the elimination and long-term surveillance of tumor cells. In a lung tumor-bearing mice model, this drug-delivery system achieved synergistic antitumor efficacy and prolonged the survival of mice.

Characteristics of the paravertebral muscle in adult degenerative scoliosis with PI-LL match or mismatch and risk factors for PI-LL mismatch.

Objective: Pelvic incidence (PI) minus the lumbar lordosis (LL) angle (PI-LL) correlates with function and disability. It is associated with paravertebral muscle (PVM) degeneration and is a valuable tool for surgical planning of adult degenerative scoliosis (ADS). This study aims to explore the characteristics of PVM in ADS with PI-LL match or mismatch and to identify the risk factors for PI-LL mismatch. Methods: A total of 67 patients with ADS were divided into PI-LL match and mismatch groups. The visual analog scale (VAS), symptom duration, and Oswestry disability index (ODI) were used to assess patients' clinical symptoms and quality of life. The percentage of fat infiltration area (FIA%) of the multifidus muscle at the L1-S1 disc level was measured by using MRI with Image-J software. Sagittal vertical axis, LL, pelvic tilt (PT), PI, sacral slope, and the asymmetric and average degeneration degree of the multifidus were recorded. Logistic regression analysis was done to identify the risk factors for PI-LL mismatch. Results: In the PI-LL match and mismatch groups, the average FIA% of the multifidus on the convex side was less than that on the concave side (P < 0.05). There was no statistical difference of asymmetric degeneration degree of the multifidus between the two groups (P > 0.05). In the PI-LL mismatch group, the average degeneration degree of the multifidus, VAS, symptom duration, and ODI were significantly higher than that in the PI-LL match group, respectively (32.22 ± 6.98 vs. 26.28 ± 6.23 (%), 4.33 ± 1.60 vs. 3.52 ± 1.46, 10.81 ± 4.83 vs. 6.58 ± 4.23 (month), 21.06 ± 12.58 vs. 12.97 ± 6.49, P < 0.05). The average degeneration degree of the multifidus muscle was positively correlated with the VAS, symptom duration, and ODI, respectively (r = 0.515, 0.614, and 0.548, P < 0.05). Sagittal plane balance, LL, PT, and the average degeneration degree of the multifidus were the risk factors for PI-LL mismatch (OR: 15.447, 95% CI: 1.274-187.269; OR: 0.001, 95% CI: 0.000-0.099; OR: 107.540, 95% CI: 5.195-2,225.975; OR: 52.531, 95% CI: 1.797-1,535.551, P < 0.05). Conclusion: The PVM on the concave side was larger than that on the convex side in ADS irrespective of whether PI-LL matched or not. PI-LL mismatch could aggravate this abnormal change, which is an important cause of pain and disability in ADS. Sagittal plane imbalance, decreased LL, higher PT, and larger average degeneration degree of the multifidus were independent risk factors for PI-LL mismatch.

Low-intensity pulsed ultrasound ameliorates depression-like behaviors in a rat model of chronic unpredictable stress.

INTRODUCTION: There is an unmet need for better nonpharmaceutical treatments for depression. Low-intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. OBJECTIVE: The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. METHODS: Chronic unpredictable stress (CUS) was used to generate rats with depression-like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression-like behaviors were assessed with the sucrose preference, forced swim, and open field tests. BDNF/mTORC1 signaling was examined by Western blot to investigate this potential molecular mechanism. The safety of LIPUS was evaluated using hematoxylin-eosin and Nissl staining. RESULTS: Four weeks of LIPUS stimulation significantly increased sucrose preference and reduced forced swim immobility time in CUS rats. LIPUS also partially reversed the molecular effects of CUS that included decreased levels of BDNF, phosphorylated tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), mammalian target of rapamycin complex 1 (mTORC1), and S6 kinase (S6K). Moreover, histological staining revealed no gross tissue damage. CONCLUSIONS: Chronic LIPUS stimulation can effectively and safely improve depression-like behaviors in CUS rats. The underlying mechanisms may be related to enhancement of BDNF/ERK/mTORC1 signaling pathways in the prefrontal cortex (PFC). LIPUS is a promising noninvasive neuromodulation tool that merits further study as a potential treatment for depression.