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The American Journal of the Medical... Jun 2024Non-small cell lung cancer (NSCLC) is a pernicious tumor with high incidence and mortality rates. The incidence rate of NSCLC increases with age and poses a serious...
BACKGROUND AND OBJECTIVE
Non-small cell lung cancer (NSCLC) is a pernicious tumor with high incidence and mortality rates. The incidence rate of NSCLC increases with age and poses a serious danger to human health. The aim of this study was to determine the mechanism by which (-)-epicatechin (EC) alleviates NSCLC.
METHODS
Twenty-four pairs of NSCLC tissues and cancer-adjacent tissues were collected, and A549 and H460 radiotherapy-resistant strains were generated by repeatedly irradiating A549 and H460 cells with dose-gradient X-rays. Radiotherapy-resistant H460 cells were successfully injected subcutaneously into the left dorsal side of nude mice at a dose of 1 × 10 to establish an NSCLC animal model. The levels of interrelated genes and proteins were detected by RT‒qPCR and Western blotting, and cell proliferation and apoptosis were evaluated by CCK‒8 assay, Transwell assay, flow cytometry, and TUNEL staining.
RESULTS
LOC107986454 was highly expressed in NSCLC patients, while miR-143-3p was expressed at low levels and was negatively correlated with LOC107986454. Functionally, EC promoted autophagy and apoptosis induced by radiotherapy, restrained cell proliferation and migration, and ultimately enhanced the radiosensitivity of NSCLC cells. A downstream mechanistic study showed that EC facilitated miR-143-3p expression by inhibiting LOC107986454 and then restraining the expression of EZH2, which ultimately facilitated autophagy and apoptosis in cancer cells, inhibited proliferation and migration, and enhanced the radiosensitivity of NSCLC cells.
CONCLUSION
EC can enhance the radiosensitivity of NSCLC cells by regulating the LOC107986454/miR-143-3p/EZH2 axis.
PubMed: 38944201
DOI: 10.1016/j.amjms.2024.06.027 -
NeuroImage Jun 2024Research indicates that hearing loss significantly contributes to tinnitus, but it alone doesn't fully explain its occurrence, as many people with hearing loss do not...
Research indicates that hearing loss significantly contributes to tinnitus, but it alone doesn't fully explain its occurrence, as many people with hearing loss do not experience tinnitus. To identify a secondary factor for tinnitus generation, we examined a unique dataset of individuals with intermittent chronic tinnitus, who experience fluctuating periods of tinnitus. EEGs of healthy controls were compared to EEGs of participants who reported perceiving tinnitus on certain days, but no tinnitus on other days.. The EEG data revealed that tinnitus onset is associated with increased theta activity in the pregenual anterior cingulate cortex and decreased theta functional connectivity between the pregenual anterior cingulate cortex and the auditory cortex. Additionally, there is increased alpha effective connectivity from the dorsal anterior cingulate cortex to the pregenual anterior cingulate cortex. When tinnitus is not perceived, differences from healthy controls include increased alpha activity in the pregenual anterior cingulate cortex and heightened alpha connectivity between the pregenual anterior cingulate cortex and auditory cortex. This suggests that tinnitus is triggered by a switch involving increased theta activity in the pregenual anterior cingulate cortex and decreased theta connectivity between the pregenual anterior cingulate cortex and auditory cortex, leading to increased theta-gamma cross-frequency coupling, which correlates with tinnitus loudness. Increased alpha activity in the dorsal anterior cingulate cortex correlates with distress. Conversely, increased alpha activity in the pregenual anterior cingulate cortex can transiently suppress the phantom sound by enhancing theta connectivity to the auditory cortex. This mechanism parallels chronic neuropathic pain and suggests potential treatments for tinnitus by promoting alpha activity in the pregenual anterior cingulate cortex and reducing alpha activity in the dorsal anterior cingulate cortex through pharmacological or neuromodulatory approaches.
PubMed: 38944171
DOI: 10.1016/j.neuroimage.2024.120713 -
Pain Medicine (Malden, Mass.) Jun 2024Neck pain and headaches can arise from the lateral atlanto-axial joint (LAA joint). This pain can be diagnosed with intra-articular injections of local anesthetic. A...
BACKGROUND
Neck pain and headaches can arise from the lateral atlanto-axial joint (LAA joint). This pain can be diagnosed with intra-articular injections of local anesthetic. A widely used technique for access to the lateral atlanto-axial joint uses a posterior approach, but this approach can be hazardous because of the proximity of the vertebral artery, the dural sac, and the C2 spinal nerve and dorsal root ganglion.
OBJECTIVE
The objective was to describe and test a new technique for accessing the LAA joint that avoids structures that lie behind the joint.
INTERVENTIONS
The new technique was described, and tested for tolerance in 10 patients with unilateral suboccipital pain, and tenderness over the LAA joint, along with evidence of LAA joint arthropathy on SPECT CT. The technique requires inserting a needle along a trajectory tangential to the dorsal surface of the C2 lamina. It involves obtaining a declined view of the C2 lamina and C2 pedicle.
CONCLUSIONS
In all cases, the C2 pedicle was easily identified and allowed the needle to pass asymptomatically underneath the neurovascular structures behind the joint. The tactile response of the lamina of C2 provided important feedback regarding needle depth caudal to the LAA joint.
PubMed: 38944030
DOI: 10.1093/pm/pnae057 -
Asian Journal of Endoscopic Surgery Jul 2024Lesser omental hernias are rare; however, they should be considered in symptomatic bowel obstruction subsequent to a subtotal or total colectomy. This report describes...
Laparoscopically treated bowel obstruction secondary to a lesser omental hernia resulting from a previous laparoscopic total colectomy for ulcerative colitis: A report of two cases.
Lesser omental hernias are rare; however, they should be considered in symptomatic bowel obstruction subsequent to a subtotal or total colectomy. This report describes two cases of recurrent bowel obstruction secondary to lesser omental hernias after laparoscopic total colectomies for ulcerative colitis. Initially, these patients had been treated conservatively; however, due to symptom recurrence, surgical intervention was decided on. In both cases, laparoscopic surgery revealed lesser omental hernias. The small bowel, which had entered from the dorsal aspect of the stomach, was returned to the original position, and the lesser omentum was closed. The patients were discharged uneventfully, with no recurrent bowel obstruction during the follow-up period. These cases highlight the importance of including internal hernias in the differential diagnosis relative to recurrent bowel obstruction, in patient subpopulations with a prior history of a subtotal or total colectomy. Confirmation by computed tomography is preferable.
Topics: Humans; Colitis, Ulcerative; Laparoscopy; Colectomy; Intestinal Obstruction; Omentum; Male; Female; Adult; Middle Aged; Peritoneal Diseases; Postoperative Complications
PubMed: 38943365
DOI: 10.1111/ases.13347 -
Pain Practice : the Official Journal of... Jun 2024In high-frequency spinal cord stimulation anatomic placement targeting of the T9-10 disc space is based on "empiric" results that are best replicated with coverage...
INTRODUCTION
In high-frequency spinal cord stimulation anatomic placement targeting of the T9-10 disc space is based on "empiric" results that are best replicated with coverage broadly from T8 to T10. This study contains the largest cohort of patients evaluating low thoracic morphology and seeks to address the lack of MRI morphological analysis in literature.
METHODS
This study was a retrospective review of a database of 101 consecutive patients undergoing permanent implant of thoracic SCS for chronic pain. Measurements were carried out on preoperative MRI imaging. Anteroposterior (AP) and lateral dimensions of the spinal cord as well as dural sac were measured. In addition, dorsal cerebrospinal fluid thickness and paddle depression distance were also measured.
RESULTS
When comparing morphological dimensions by level, dorsal CSF thickness was smaller at T9-10 than T7-8 (p = 0.018). In addition, lateral dural and spinal cord diameters were larger at T10-11 than T9-10, contributing to larger dural surface area at T10-11 (p = 0.028). While trends of dorsal CSF thickness tend to decrease with lower thoracic levels, the ratio of surface area of spinal cord to dural sac appeared to remain relatively constant.
CONCLUSIONS
Dorsal CSF thickness is smaller at T9-10 than T7-8 in chronic pain patients in this cohort. More ellipsoid, cord, and spinal canal diameter measurements were noted at lower levels of the thoracic spinal cord, particularly at T10-11. This may correlate with anatomical SCS placement. Future studies should evaluate efficacy of SCS therapy for pain based on these anatomical considerations.
PubMed: 38943345
DOI: 10.1111/papr.13398 -
Stem Cells and Development Jun 2024Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally...
Adipose stem cells are considered one of the primary drivers of autologous fat graft biologic activity and survival. We have previously demonstrated that hormonally active VD3 improved adipose stem cell viability in ex vivo and in vivo fat grafting models. In this study, we evaluated the inactive form of VD3 (cholecalciferol) on adipose stromal cell (ASC) phenotype during hypoxia and the subsequent effect on human fat graft retention in the xenograft model. Lipoaspirate collected from six human donors was used for ex-vivo particle culture studies and isolated ASC studies. Adipose particles were treated with increasing doses of VD3 to determine impact on ASC survival. Expanded stromal cells were treated with VD3 during hypoxic culture and assessed for viability, apoptosis, mitochondrial activity, and nitric oxide release via caspase, DAF-FM, or TMRM. Finally, forty Nu/J mice receiving bilateral dorsal human lipoaspirate were treated thrice weekly with 1) Vehicle control, 2) 50ng calcitriol, 3) 50ng VD3, 4) 500ng VD3, and 5) 5000ng VD3 for 12 weeks, n=8 per group. Graft weight, volume, and architecture were analyzed. Adipose particles treated with dose escalating VD3 had significantly increased ASC viability compared to control (p<0.01). Under hypoxia, ASCs treated with 1nM VD3 had significantly greater viability than untreated and pre-treated cells (p<0.01, p<0.01) and significantly lower apoptosis-to-viability ratio (p<0.01). ASCs pre-treated with 1nM VD3 had significantly lower nitric oxide release (p<0.05) and lower mitochondrial polarization (p<0.05) compared to controls. In vivo results showed mice receiving 5000ng VD3 had significantly greater graft weight (p<0.05) and volume (p<0.05) after 12 weeks of treatment compared to controls. Grafts had enhanced neovascularization, intact adipocyte architecture, and absence of oil cysts. VD3 is an over-the-counter nutritional supplement with a known safety profile in humans. Our xenograft model suggests administering VD3 at the time of surgery may significantly improve fat graft retention.
PubMed: 38943277
DOI: 10.1089/scd.2024.0056 -
Journal of Neurovirology Jun 2024The Rabies virus is a neurotropic virus that manipulates the natural cell death processes of its host to ensure its own survival and replication. Studies have shown that...
The Rabies virus is a neurotropic virus that manipulates the natural cell death processes of its host to ensure its own survival and replication. Studies have shown that the anti-apoptotic effect of the virus is mediated by one of its protein named, rabies glycoprotein (RVG). Alzheimer's disease (AD) is characterized by the loss of neural cells and memory impairment. We aim to examine whether expression of RVG in the hippocampal cells can shield the detrimental effects induced by Aβ. Oligomeric form of Aβ (oAβ) or vehicle was bilaterally microinjected into the dorsal hippocampus of male Wistar rats. One week later, two μl (10 T.U. /ml) of the lentiviral vector carrying RVG gene was injected into their dorsal hippocampus (post-treatment). In another experiment, the lentiviral vector was microinjected one week before Aβ injection (pre-treatment). One week later, the rat's brain was sliced into cross-sections, and the presence of RVG-expressing neuronal cells was confirmed using fluorescent microscopy. Rats were subjected to assessments of spatial learning and memory as well as passive avoidance using the Morris water maze (MWM) and the Shuttle box apparatuses, respectively. Protein expression of AMPA receptor subunit (GluA1) was determined using western blotting technique. In MWM, Aβ treated rats showed decelerated acquisition of the task and impairment of reference memory. RVG expression in the hippocampus prevented and restored the deficits in both pre- and post- treatment conditions, respectively. It also improved inhibitory memory in the oAβ treated rats. RVG increased the expression level of GluA1 level in the hippocampus. Based on our findings, the expression of RVG in the hippocampus has the potential to enhance both inhibitory and spatial learning abilities, ultimately improving memory performance in an AD rat model. This beneficial effect is likely attributed, at least in part, to the increased expression of GluA1-containing AMPA receptors.
PubMed: 38943023
DOI: 10.1007/s13365-024-01221-y -
Scientific Reports Jun 2024In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen....
In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1-10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca channels responsible for the cardiac action potentials depolarization phase. Two types of Ca currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.
Topics: Animals; Bees; ortho-Aminobenzoates; Myocytes, Cardiac; Insecticides; Cardiotoxicity; Calcium; Myocardial Contraction; Heart; Ryanodine Receptor Calcium Release Channel; Diamide
PubMed: 38942905
DOI: 10.1038/s41598-024-65007-2 -
The Journal of Neuroscience : the... Jun 2024During navigation, the neocortex must actively integrate learned spatial context with current sensory experience to guide behaviours. However, the relative encoding of...
During navigation, the neocortex must actively integrate learned spatial context with current sensory experience to guide behaviours. However, the relative encoding of spatial and sensorimotor information among cortical cells, and whether hippocampal feedback continues to modify these properties in familiar environments, remains poorly understood. Thus, two-photon microscopy of male and female Thy1-GCaMP6s mice was used to longitudinally image neurons spanning superficial retrosplenial cortex and layers II-Va of primary and secondary motor cortices before and after bilateral dorsal hippocampal lesions. During behaviour on a familiar cued treadmill, the locations of two added obstacles were interchanged to decouple place-tuning from cue-tuning among the position correlated cells with fields at those locations. The subpopulations of place- and cue-tuned cells each formed interareal gradients such that higher-level cortical regions exhibited higher fractions of place cells, whereas lower-level regions exhibited higher fractions of cue cells. Position correlated cells in motor cortex also formed translaminar gradients; cells closer to the cortical surface were more likely to exhibit fields and were more sparsely and precisely tuned than deeper cells. After dorsal hippocampal lesions, a neural representation of the learned environment persisted but retrosplenial cortex exhibited significantly increased cue-tuning and, in motor cortices, both position correlated cell recruitment and population activity at the unstable obstacle locations became more homogeneously elevated across laminae. Altogether, these results support that the hippocampus continues to modulate cortical responses in familiar environments, and the relative impact of top-down feedback obeys hierarchical interareal and interlaminar gradients opposite to the flow of bottom-up sensory inputs. During learning, the hippocampus imparts spatial context to memory representations throughout the superficial neocortex. However, the post-learning role of the hippocampus has not been well defined. The results of this study suggest that, during navigation of a familiar environment, the hippocampus continues to link unreliable sensory attributes to a stable contextual framework, effectively updating the learned model of the environment. The results are also consistent with top-down suppression of sensory-evoked activity during behaviour, which varied in strength according to hierarchical proximity to the hippocampus. This effect was abolished by bilateral lesions of the dorsal hippocampus, supporting that the hippocampus plays an ongoing role in propagating context-dependent predictions throughout the cortical hierarchy, a core hypothesis of the predictive coding theoretical framework.
PubMed: 38942472
DOI: 10.1523/JNEUROSCI.1619-23.2024 -
Regional Anesthesia and Pain Medicine Jun 2024The efficacy of spinal cord stimulation (SCS) in chronic pain studies is traditionally assessed by pain scores, which do not reflect the multidimensional nature of pain... (Review)
Review
BACKGROUND
The efficacy of spinal cord stimulation (SCS) in chronic pain studies is traditionally assessed by pain scores, which do not reflect the multidimensional nature of pain perception. Despite the evidence of SCS's influence on emotional functioning comprehensive assessments of its effect remain lacking.
OBJECTIVE
To assess changes in emotional and psychosocial functioning in patients who underwent SCS implantation for chronic pain.
EVIDENCE REVIEW
Ovid MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and Scopus databases were searched for original peer-reviewed publications reporting emotional functioning after SCS. The primary outcomes were a pooled mean difference (MD) in anxiety, depression, global functioning, mental well-being and pain catastrophizing at 12 months. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to determine the quality of evidence.
FINDINGS
Thirty-two studies were included in the primary analysis. Statistically significant improvements were observed in anxiety (MD -2.16; 95% CI -2.84 to -1.49; p<0.001), depression (MD -4.66; 95% CI -6.26 to -3.06; p<0.001), global functioning (MD 20.30; 95% CI 14.69 to 25.90; p<0.001), mental well-being (MD 4.95; 95% CI 3.60 to 6.31; p<0.001), and pain catastrophizing (MD -12.09; 95% CI -14.94 to -9.23; p<0.001). Subgroup analyses revealed differences in Global Assessment of Functioning and mental well-being based on study design and in depression based on waveform paradigm.
CONCLUSION
The results highlight the statistically and clinically significant improvements in emotional and psychosocial outcomes in patients with chronic pain undergoing SCS therapy. However, these results need to be interpreted with caution due to the very low certainty of evidence per the GRADE criteria.
PROSPERO REGISTRATION
CRD42023446326.
PubMed: 38942426
DOI: 10.1136/rapm-2024-105523