ABSTRACT
Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Subject(s)
Humans , Neoplasms/pathology , Immunotherapy/methods , Immune Checkpoint Inhibitors/therapeutic useABSTRACT
Objective To investigate the therapeutic effect of hydrogel-encapsulated human umbilical cord mesenchymal stem cells (hUC-MSCs) on traumatic brain injury in rats and its related mechanism. Methods SD rat models of traumatic brain injury were constructed, which were divided into control group, chitosan group, stem cell group and combined treatment group. Results During the treatment, there was no significant difference in mNSS score between the control group and the chitosan group (P>0.05). On the 15th, 22nd, 29th and 36th day, the mNSS score of the combined treatment group decreased most significantly than that of the control group, followed by the stem cell group (P0.05), and the expression of related proteins in the stem cell group and the combined treatment group increased significantly. The expression level of the related protein in the combined treatment group was the highest, followed by stem cell group, the lowest in the control group and chitosan group (P<0.05). Conclusion Compared with stem cell transplantation alone, hydrogel-encapsulated hUC-MSCs transplantation can improve the motor and learning and memory abilities of rats with traumatic brain injury more effectively.
ABSTRACT
[ABSTRACT]OBJECTIVETo investigate the relationships between electrophysiological characteristic of speech evoked auditory brainstem response and Mandarin phonetically balanced maximum, so as to provide more clues for the mechanism of speech cognitive behavior. METHODSThe speech discrimination scores were obtained by Mandarin phonemic-balanced monosyllable lists via speech audiometric software in forty-one ears of normal hearing adults. Their s-ABRs were recorded with speech syllables da with the intensity of phonetically balanced maximum (PBmax). The electrophysiological characteristic of s-ABR, as well as the relationships between PBmax and s-ABR parameters including latency in time domain, fundamental frequency (F0) and first formant (F1) in frequency domain were analyzed statistically.RESULTS While divided the subjects into three groups by PBmax1= 100%, 100%
ABSTRACT
OBJECTIVE@#To investigate the relationships of electrophysiological characteristics between speech evoked auditory brainstem response (s-ABR) and auditory mismatch negativity (MMN), so as to provide more clues for the mechanism of speech cognitive behavior.@*METHOD@#Thirty-three ears in 33 normal hearing adults were included in this study. Their s-ABR were recorded with speech syllables /da/ at 80 dB HL intensity. Meanwhile, two MMNs were recorded with 1 kHz frequency deviant extent and 40 dB intensity deviant extent in them. The electrophysiological characteristics of s-ABRs and MMNs, as well as the relationships of MMN latencies between s-ABR parameters including latencies in time domain, fundamental frequency(F0) and first formants(F1) in frequency domain were analyzed statistically.@*RESULT@#MMN latency of frequency deviance showed a negative correlation tendency with s-ABR transient components, and it showed a positive trend with sustained components of s-ABR. While MMN latency of intensity deviance showed a positive correlation with s-ABR latency of peak V, A and D respectively, and it negatively showed a correlation with s-ABR latency of other peak s and amplitude of F0 and FI respectively. Only the s-ABR latency of peak F and MMN latency of frequency deviance, and the F0 amplitude of s-ABR and MMN latency of intensity deviance were moderate correlation statistically.@*CONCLUSION@#It was probably the neurons of frequency deviant MMN unmatched the characteristics of frequency with the neurons of s-ABR transient component, but well matched the characteristics of frequency with the neurons of s-ABR sustained component. Similarly, the neurons of intensity deviant MMN probably matched the characteristics of intensity with neurons of different components of s-ABR or not. These results may formed as a valuable clue for further investigation of speech perception and temporal processing abilities.
Subject(s)
Adult , Humans , Acoustic Stimulation , Evoked Potentials, Auditory, Brain Stem , Speech , Speech PerceptionABSTRACT
Objective To investigate the neuroprotective mechanism of cerebral ischemic preconditioning by detecting the expression changes of hippocampus nuclear factor-κB (NF-κB) and Hesl mRNA after cerebral ischemia-reperfusion in rats.Methods A total of 108 healthy male SD rats were randomly divided into a cerebral ischemia group,a cerebral ischemic preconditioning group,and a sham operation group,and then redivided into 22 h,48 h,72 h,7 d,and 14 d subgroups.Ischemic preconditioning was performed at day 3 before establishing the cerebral ischemia-reperfusion injury model by transient occlusion of right internal carotid artery for 10 min.At each time point after cerebral ischemia-reperfusion,the neurological deficit score and cerebral infarction volume measurement were performed,and the expressions of NF-κB and Hes1 mRNA in the hippocampus were detected by using real-time fluorescence quantitative polymerase chain reaction.Results The neurological function scores and the percentage of cerebral infarction volume in the cerebral ischemic preconditioning goup at each time point were significantly lower than those in the cerebral ischemia-reperfusion group (all P ＜0.05).The expression levels of NF-κB and Hesl mRNAs in each group had progressive reduction with time.Compared with the same time point,it showed that the expression levels of NF-κB and Hes1 mRNAs in the cerebral ischemic preconditioning group and the cerebral ischemia-reperfusion group were significantly higher than those in the sham operation group,the expression level of NF-κB mRNA in the cerebral ischemic preconditioning group was significantly lower than that in the cerebral ischemia-reperfusion group,and the expression level of Hesl mRNA was significantly higher than that in the cerebral ischemia-reperfusion group (all P ＜0.05).Conclusions The upregulation of Hesl and down-regulation of NF-κB may be involved in the neuroprotective mechanisms of cerebral ischemic preconditioning.