The complement (C) innate immune system has been shown to be activated in the tumor microenvironment of various cancers. The C may support tumor growth by modulating the immune response and promoting angiogenesis through the actions of C anaphylatoxins (e.g., C5a, C3a). The C has important double-edged sword functions in the brain, but little is known about its role in brain tumors. Hence, we analyzed the distribution and the regulated expression of C3a and its receptor C3aR in various primary and secondary brain tumors. We found that C3aR was dramatically upregulated in Grade 4 diffuse gliomas, i.e., glioblastoma multiforme, IDH-wildtype (GBM) and astrocytoma, IDH-mutant, Grade 4, and was much less expressed in other brain tumors. C3aR was observed in tumor-associated macrophages (TAM) expressing CD68, CD18, CD163, and the proangiogenic VEGF. Robust levels of C3a were detected in the parenchyma of GBM as a possible result of Bb-dependent C activation of the alternative C pathway. Interestingly, in vitro models identified TGF-β1 as one of the most potent growth factors that upregulate VEGF, C3, and C3aR in TAM (PMA-differentiated THP1) cell lines. Further studies should help to delineate the functions of C3a/C3aR on TAMs that promote chemotaxis/angiogenesis in gliomas and to explore the therapeutic applications of C3aR antagonists for brain tumors.
Background: Chronic non-specific neck pain (CINP) is common, but the etiology remains unclear. This study aimed to examine the relationship between cervical muscle composition (cervical multifidus and longus capitis/longus colli), morphometry, range of movement, muscle function, and disability severity (Neck Disability Index) in patients with CINP. Methods: From September 2020 to July 2021, subjects underwent cervical MRI and clinical tests (cervical range of motion, cranio-cervical flexion test, neck flexor, and extensor muscle endurance). MRI analysis comprised muscle cross-sectional area, volume, and fat infiltration of multifidus and longus colli between C4 and C7 levels. Results: Twenty-five participants were included. Multiple linear regression analysis indicated that NDI was positively correlated with the volume percentage of fat infiltration of the multifidus (B = 0.496), negatively correlated with fat-free muscle volume of the multifidus normalized by subject height (B = −0.230), and accounted for 32% of the variance. There was no relationship between neck disability and longus capitis/longus colli morphology. We also found no relationship between neck disability scores, neck flexor or extensor muscle endurance, or the outcome motor control test of craniocervical flexion (p > 0.05). Conclusions: Neck disability was moderately correlated with the percentage of fat volume in the multifidus muscle and fat-free volume of the multifidus. There was no relationship between NDI scores and muscle function test outcomes or any fat or volume measures pertaining to the longus colli muscle.
Cervical proprioception plays a key role in postural control, but its specific contribution is controversial. Postural impairment was shown in whiplash injuries without demonstrating the sole involvement of the cervical spine. The consequences of degenerative cervical spine diseases are underreported in posture-related scientific literature in spite of their high prevalence. No report has focused on the two different mechanisms underlying cervicobrachial pain: herniated discs and spondylosis. This study aimed to evaluate postural control of two groups of patients with degenerative cervical spine diseases with or without optokinetic stimulation before and after surgical treatment. Seventeen patients with radiculopathy were recruited and divided into two groups according to the spondylotic or discal origin of the nerve compression. All patients and a control population of 31 healthy individuals underwent a static posturographic test with 12 recordings; the first four recordings with the head in 0° position: eyes closed, eyes open without optokinetic stimulation, with clockwise and counter clockwise optokinetic stimulations. These four sensorial situations were repeated with the head rotated 30° to the left and to the right. Patients repeated these 12 recordings 6weeks postoperatively. None of the patients reported vertigo or balance disorders before or after surgery. Prior to surgery, in the eyes closed condition, the herniated disc group was more stable than the spondylosis group. After surgery, the contribution of visual input to postural control in a dynamic visual environment was reduced in both cervical spine diseases whereas in a stable visual environment visual contribution was reduced only in the spondylosis group. The relative importance of visual and proprioceptive inputs to postural control varies according to the type of pathology and surgery tends to reduce visual contribution mostly in the spondylosis group.