Background:
Cancer cachexia is a common but severe condition that causes muscle wasting, body weight loss, and progressive functional impairment, affecting over 50% of cancer patients. Currently, ...there are no effective treatments that can alleviate cachexia, and hence the discovery of new therapeutics that can effectively prevent or even reverse cancer cachexia is crucial. Babao Dan (BBD) is a Traditional Chinese Medicine (TCM) formula that has been used clinically in combating various cancers, however, its therapeutic potential in alleviating cancer cachexia remains unexplored. Our current study aims to determine the anti-cachectic effects of BBD treatment in alleviating cancer cachexia, as well as determining the underlying mechanisms involved.
Methods:
Mouse models of cancer cachexia were induced via implantation of CT26 colon adenocarcinoma cells, and the anti-cachectic effects and mechanisms of BBD were determined via examinations of body weight and muscle mass, as well as serum and muscle markers of cachexia and muscle atrophy.
Results:
CT26 tumor implantation reduced in the rapid occurrence of cancer cachexia characterized by marked reductions in body weight and muscle mass, functional decrease in muscle function and accelerated deaths. BBD administration not only demonstrated robust anti-cachectic ability via preventing decreases in body weight, muscle mass, and muscle atrophy, but also markedly prolonged survival. The effects of BBD in alleviating cancer cachexia and its associated adverse effects were due to its ability in preventing the activation of IL-6/STAT3 signaling post-CT26 tumor implantation.
Conclusion:
Our findings demonstrated the robust ability of BBD in preventing cancer cachexia and alleviating the main cachexia-induced symptoms as well as prolonging survival via inhibiting activation of IL-6/STAT3 signaling pathway. Therefore, our study demonstrating the strong anti-cachectic effects of BBD in mice may provide a theoretical basis for the use of BBD as a safe and effective drug in the treatment of cancer cachexia.
Enhancers can act as cis-regulatory elements to control transcriptional regulation by recruiting transcription factors (TFs) in a distance and orientation-independent manner. However, it is still ...unclear how p53 participates in the enhancer network as TF in hepatic carcinoma under the condition of DNA damage. A total of 14,286 active enhancers were identified through the integration of stable and unstable enhancer RNAs (eRNAs) captured by CAGE and GRO-seq, respectively. Furthermore, 218 p53-bound enhancers (Enh
p53
) were identified by analyzing p53 ChIP-seq in HepG2 cells after DNA damage. The results showed that the enhancer expression and histone markers of enhancers (H3K4me1, H3K4me2, H3K4me3, H3K9ac, and H3K27ac) revealed significantly higher level on Enh
p53
than Enh
no−p53
which suggested that p53 participated in regulating enhancer activity and chromatin structure. By analyzing 124 TFs ChIP-seq from ENCODE, 93 TFs were found significantly enriched on Enh
p53
such as GATA4, YY1, and CTCF, indicating p53 may co-regulate enhancers with TFs participation. Moreover, significantly differentially expressed 438 miRNAs and 1,264 mRNAs were identified by analyzing small RNA-seq and RNA-seq, and 26 Enh
p53
-miRNAs and 145 Enh
p53
-mRNA interactions were identified by the integration of 3D genome data and genomic distance. The functional enrichment analysis showed that these miRNA targets and mRNAs were significantly involved in tumor biological processes and signaling pathways such as DNA replication, p53 signaling pathway, hepatitis B, focal adhesion, etc. The above results indicated that p53 participated in regulating enhancer network in hepatic carcinoma and Enh
p53
exhibited significantly different characteristics with Enh
no−p53
.
Toll-like receptor 9 (TLR9) recognises unmethylated CpG DNA and activates a signalling cascade, leading to the production of inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-12 via the adaptor ...protein MyD88. However, the specific sequence and structural requirements of the CpG DNA for the recognition of and binding to TLR9 are unknown. Moreover, the 3D structures of TLR9 and the TLR9-ODN complex have not been determined. In this study, we propose a reliable model of the interaction of the TLR9 ECD with CpG ODN using bioinformatics tools.
The three-dimensional structures of two TLR9 ECD-CpG ODN complexes were constructed using a homology modelling and docking strategy. Based on the models of these complexes, the TLR9 ECD-CpG ODN interaction patterns were calculated. The results showed that the interface between the human TLR9 and the CpG ODN molecule is geometrically complementary. The computed molecular interactions indicated that LRR11 is the main region of TLR9 that binds to CpG ODN and that five positively charged residues within LRR11 are involved in the binding of the TLR9 ECD to the CpG ODN. Observations in the close-up view of these interactions indicated that these five positively charged residues contribute differently to the binding region within the TLR9 ECD-CpG ODN complex. 337Arg and 338Lys reside in the binding sites of ODN, forming hydrogen bonds and direct contacts with the CpG ODN, whereas 347Lys, 348Arg, and 353His do not directly contact the CpG ODN. These results are in agreement with previously reported experimental data.
In this study, we present two structural models for the human and mouse TLR9 ECD in a complex with CpG ODN. Some features predicted by this model are consistent with previously reported experimental data. This complex model may lead to a better understanding of the function of TLR9 and its interaction with CpG ODN and will improve our understanding of TLR9-ligand interaction in general.
The glycoprotein D (gD) is essential for Herpes B virus (BV) entry into mammalian cells. Nectin-1, an HSV-1 gD receptor, is found to be the receptor which mediated BV induced cell-cell fusion, while ...HVEM does not mediate fusion by BV glycoprotein. However, the specific sequence and structural requirements of the BV gD for the recognition of and binding to Nectin-1 are unknown. Moreover, the 3D structures of BV gD and the BV gD-receptor complex have not been determined. In this study, we propose a reliable model of the interaction of the BV gD with receptor using bioinformatics tools.
The three-dimensional structures of two BV gD-receptor complexes were constructed using homology modelling and docking strategy. Based on the models of these complexes, the BV gD receptor interaction patterns were calculated. The results showed that the interface between the BV gD and nectin-1 molecule is not geometrically complementary. The computed molecular interactions indicated that two terminal extensions were the main region of BV gD that binds to nectin-1 and that hydrophobic contacts between the two molecules play key roles in their recognition and binding. The constructed BV gD-HVEM complex model showed that this complex had a lower shape complementarity value and a smaller interface area compared with the HSV-1 gD-HVEM complex, and the number of intermolecular interactions between BV gD-HVEM were fewer than that of HSV-1 gD-HVEM complex. These results could explain why HVEM does not function as a receptor for BV gD.
In this study, we present structural model for the BV gD in a complex with its receptor. Some features predicted by this model can explain previously reported experimental data. This complex model may lead to a better understanding of the function of BV gD and its interaction with receptor and will improve our understanding of the activation of the BV fusion and entry process.
The rotational Doppler effect (RDE) of optical vortex which can be used to detect the rotation speed, has become a well-known phenomenon and a hot topic of research in recent years. However, because ...the beam axis must be coaxial with the rotational axis of the object, it can only be used to detect cooperative targets in practical application. Here, we provide a novel approach for measuring rotational speed under light non-coaxial incidence relative to the rotating axis that uses the adjacent frequency difference of rotational Doppler shift signals. Theoretically, the rotational Doppler shift is proportional to the OAM mode of the incident beam, and the nature of the OAM carried by each photon is a discrete or quantized quantity under off-axis conditions leading to the discrete distribution of the Doppler shift signals. Experimentally, by extracting the difference between two adjacent Doppler shift signals, the rotating speed of the object can be determined. Based on our method, the rotational speed of the object can be measured precisely without the pre-known information about the position of the rotating axis. Our work supplies a significant complement to the conventional RDE theory and we believe it may promote the realistic application of the optical RDE-based metrology.
The simultaneous and independent measurement of multiple movement forms is a significant issue to be solved in research. In this paper, we proposed a method that combines the self-interference of ...conjugated optical vortices and external interference of plane waves, and successfully realize the independent measurement of both rotation and rectilinear motion. Three kinds of interference schemes based on vortex beams are analyzed theoretically and verified experimentally. The results show that the double interference between conjugated optical vortices and Gaussian beam can detect the motion along and perpendicular to the beam propagation direction even under complex motion background, providing a powerful way to detect the multiple movement forms of a target. Our work may pave a new way for the detection of spatial noncooperative targets and stimulate the invention of new detection equipment.
The optical rotational Doppler effect (RDE) is closely related to the unique orbital angular momentum (OAM) carried by optical vortex, whose topological charge means the mode of OAM. Compared with ...the coaxial incidence, the rotational Doppler frequency shift spectrum of a misaligned optical vortex (misaligned RDE) widens according to a certain law. In this paper, an OAM modal decomposition method of the misaligned optical RDE is proposed and the relative intensity of different OAM modes, namely the OAM spectrum, is derived based on an inner product computation. Analyses show that lateral displacements and angular deflections change the distribution of OAM modes relative to the rotation axis of the object. A misaligned Laguerre-Gaussian (LG) vortex can be represented as a specific combination of coaxial LG modes, and the difference between the topological charge of two adjacent modes is 1 or 2 with lateral displacements or angular deflections respectively. An experiment of misaligned optical RDE using a superimposed LG vortex is executed, and the obtained frequency shift spectrum with misaligned incidence expands into a set of discrete signals, which agrees well with the theoretical results. Moreover, we can get the rotation frequency of the object from an expanded frequency spectrum more quickly and accurately based on the difference between two adjacent signal peaks. The proposed method contributes to analyze the misaligned optical RDE comprehensively, which is significant in remote sensing and optical metrology.
Rotational speed measurement has increasingly become an important requirement both in the industrial and aerospace fields. This article presents a technique for rotational speed measurement based on ...the non-contact optical method by using superposition vortex light. To the best of our knowledge, for the first time, we realized the ultralow rotational speed measurement as low as 0.001 r/s with high accuracy based on real rotating objects. By using an optical vortex (OV) with a large topological charge up to ±65, the rotational frequency is magnified significantly. The detection system proposed in this article has a simple structure and non-contact features, including a transmitter, a receiver end, and a control and signal processing unit. Depending on the rotational speed of the target, the different sampling time is used to achieve near real-time speed acquisition. The experimental results suggest that the measurement result of the rotational speed has nothing to do with the receive angle of the receiver, and different receive distances only affect the intensity of the signal. An autocorrelation algorithm is designed which can effectively improve the signal-to-noise ratio of the detection signal. At different rotation speeds, the experimental results are in good agreement with the theoretical value. Our work fills the margin of the ultralow rotational speed measurement of RDE, and the related technique in this article may be useful in the precision mechanical testing and spatial instability targets sensing.
Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury
portal veins. ...Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study.
A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats.
In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury.
The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.
The capability to detect the rotational speed of non-cooperative targets in a long distance is a difficult problem to be solved. In recent years, vortex light provides a feasible solution for the ...measurement of rotational speed for its spiral phase and the orbital angular momentum. Laguerre-Gaussian (LG) mode, as the typical vortex beam, has been widely employed in rotational Doppler effect (RDE) experiments. Here, we show that the nonzero radial index LG beam not only has a specific physical meaning but also can enhance the light intensity and the amplitude of RDE frequency signal relative to a zero radial index LG beam. To this end, we theoretically analyze the reason of intensity enhancement of a nonzero radial index beam and verify the conclusion in a variable control experiment. Our study provides a new aspect of LG beams that can be considered in rotational speed detection based on RDE. It may produce an improvement of the detection range of rotating targets in practical applications.
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