Correction: A novel nano delivery system targeting different stages of osteoclasts.

Correction for 'A novel nano delivery system targeting different stages of osteoclasts' by Bosong Zhang et al., Biomater. Sci., 2022, 10, 1821-1830, https://doi.org/10.1039/D2BM00076H.

Similarity enhances psychological compatibility: Serial mediation effect of psychological kinship and intergroup contact.

Purpose: This study elucidates the relationship between similarity and ethnic psychological compatibility and its underlying psychological mechanisms. According to kin selection theory, similarity can promote ethnic psychological compatibility by enhancing psychological kinship and intergroup contact. Participants: and methods: A questionnaire survey was administered to 1523 participants from 25 ethnic groups in China. Data analysis was carried out via conditional process modelling. A multigroup comparison of mediation models between the ethnic majority and minorities was detected via the Stats Tools Package. Results: Our findings demonstrated that: (1) cultural and attitude similarity both showed a significant positive correlation with ethnic psychological compatibility; (2) psychological kinship and intergroup contact served as mediators in the relationship of attitude and cultural similarity with ethnic psychological compatibility and psychological kinship and intergroup contact were independent mediators, while psychological kinship-intergroup contact showed a significant serial mediation effect; (3) there were no significant differences in mediation effects between different ethnic groups. Conclusion: Our findings expand on kin selection theory and provide valuable paths for psychologically supporting ethnic psychological compatibility.

Effects of Social Exclusion on Self-Evaluation: Domain Discrepancy Based on the Big Two Model.

Prior studies have demonstrated the detrimental effects of social exclusion on an individual's self-perception. Nonetheless, existing literature has predominantly focused on its impact on global self-esteem, often neglecting the nuanced effects of various reasons for social exclusion on distinct dimensions of self-evaluation, such as agency and communion. Based on the Big Two model perspective, the present research aims to examine the differential impacts of social exclusion on the distinct dimensions of self-evaluation, namely agency and communion, considering the reasons for social exclusion. It is hypothesized that social exclusion affects different facets of self-evaluation-agency and communion-depending on the context of exclusion. Study 1 identified negative correlations between perceived social exclusion and self-evaluation measures through questionnaires, including global self-esteem and the self-concepts of agency and communion, within a sample of 483 participants (283 females). Studies 2a (n = 93; 75 females) and 2b (n = 91; 66 females), which employed a recall paradigm to manipulate social exclusion in the domains of communion and agency, respectively, revealed that communion exclusion diminished communal self-evaluation, and agency exclusion significantly reduced both agentic and communal self-evaluation. These findings highlight the necessity of distinguishing various types of social exclusion and their distinct effects on the dimensions of self-concept. The research has important implications for the development of interventions aimed at enhancing individual psychological well-being and promoting inclusive social environments.

The paradox of pandemic mitigation? Moderating role of pandemic severity on the impact of social distancing policies: a cultural value perspective.

BACKGROUND: Social distancing policies were of utmost importance during the early stages of the COVID-19 pandemic. These policies aimed to mitigate the severity of local outbreaks by altering public behavior. However, if the severity of the pandemic reduces, the impact of these policies on actual behavior may decrease. This study aims to examine, from a global perspective, whether the impact of social distancing policies on actual mobility is moderated by local pandemic severity and whether this moderating effect varies across cultural value contexts. METHODS: We combined multiple publicly available global datasets for structural equation model analysis. 17,513 rows of data from 57 countries included in all databases were analyzed. Multilevel moderated moderation models were constructed to test the hypotheses. RESULTS: More stringent policies in a region mean less regional mobility (ß = -0.572, p < 0.001). However, the severity of local outbreaks negatively moderated this effect (ß = -0.114, p < 0.001). When the pandemic was not severe, the influence of policy intensity on mobility weakened. Furthermore, based on Schwartz's cultural values theory, cultural values of autonomy (ß = -0.109, p = 0.011), and egalitarianism (ß = -0.108, p = 0.019) reinforced the moderating effect of pandemic severity. On the other hand, cultural values of embeddedness (ß = 0.119, p = 0.006) and hierarchy (ß = 0.096, p = 0.029) attenuated the moderating effect. CONCLUSIONS: Social distancing policies aim to reduce the severity of local pandemics; however, the findings reveal that mitigating local pandemics may reduce their impact. Future policymakers should be alert to this phenomenon and introduce appropriate incentives to respond. The results also show that the moderating role of pandemic severity varies across cultures. When policies are promoted to deal with global crises, policymakers must seriously consider the resistance and potential incentives of cultural values.

The association between social class and aggression: A meta-analytic review.

RATIONALE: Substantial evidence links social class with aggression. Despite lower social class being recognized as a risk factor for high levels of aggression, the findings of this association have been inconsistent. Some studies have indeed illustrated that a social class level is inversely associated with aggression, while other studies have demonstrated positive or null associations. OBJECTIVE: To clarify previously inconsistent findings, this meta-analysis assesses the overall magnitude of this relationship and examines the potential moderators. METHODS: A total of 268 studies met the inclusion criteria, and we used 546 effect sizes in 357 independent samples from these studies. A random-effects meta-analytic model was employed and several moderator analyses were conducted. RESULTS: Overall, social class shared a small but significant negative relationship with aggression (r = -0.092). Moderator analyses suggested that study-level (e.g., type of study, and national differences), sample-level (e.g., age), class-level (e.g., type, assessment, and source of social class), and aggression-level (e.g., type of aggression) characteristics accounted for heterogeneity in the relationship. Additional analyses also revealed the robustness of these effects with little evidence of publication bias. CONCLUSIONS: Living in disadvantaged socioecological environments, lower-class individuals may exhibit more aggression to adapt to threats. Moreover, the relationship between social class and aggression is not fixed and can change with specific contexts, and aggression is not an essential feature of a particular social group. This research hopes to inspire future studies to explore the association between social class and aggression more thoroughly. Additionally, it provides insights into how to reduce aggression among lower-class individuals.

Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease.

Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood-brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6-RES-OPC-HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6-RES-OPC-HA nanoparticles have the potential to prevent and alleviate early AD.

Intergroup Contact Alleviates Loneliness: The Extensive Effect of Common Ingroup Identity.

Purpose: Previous studies show that intergroup contact, through common ingroup identity, has impact on intergroup processes such as reducing intergroup bias, improving intergroup relations, etc. The effect of intergroup contact on individual psychological process (through common ingroup identity), however, needs further exploration. Based on the positive effect of both intergroup contact and ingroup identification on mental health and well-being, this article proposes and tests a new model of individual loneliness reduction through intergroup contact by promoting common ingroup identity. Methods: A total of 263 majority ethnic members and 275 minority ethnic members from China participated in the survey. Intergroup contact, common ingroup identity and loneliness were measured at three time-points (T1-T3) over an 8-month period. Longitudinal mediation analysis and parallel process Latent Growth Curve Model for mediation are used for the examination of the indirect effect of common ingroup identity. Results: Longitudinal mediation analysis showed that intergroup contact quality at T1 positively predicted common ingroup identity at T2, and common ingroup identity at T2 alleviated loneliness at T3. Intergroup contact quality at T1 was indirectly linked to loneliness at T3 via common ingroup identity at T2. The parallel process latent growth curve model for mediation confirmed the robustness of the indirect effect of common ingroup identity. In addition, the growth rate of the quality of intergroup contact increased the growth rate of common ingroup identity, but reduced the growth rate of loneliness. Conclusion: The current study revealed the protectiveness of intergroup contact and common ingroup identity on loneliness, viz., intergroup contact reduces individual loneliness by promoting common ingroup identity, the implication being that intergroup contact and common ingroup identity should be taken into account in intervening process of loneliness prevention so that an individual's physical and mental health could be better safeguarded.

The KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling during cardiac hypertrophy in male mice.

The main hallmark of myocardial substrate metabolism in cardiac hypertrophy or heart failure is a shift from fatty acid oxidation to greater reliance on glycolysis. However, the close correlation between glycolysis and fatty acid oxidation and underlying mechanism by which causes cardiac pathological remodelling remain unclear. We confirm that KLF7 simultaneously targets the rate-limiting enzyme of glycolysis, phosphofructokinase-1, liver, and long-chain acyl-CoA dehydrogenase, a key enzyme for fatty acid oxidation. Cardiac-specific knockout and overexpression KLF7 induce adult concentric hypertrophy and infant eccentric hypertrophy by regulating glycolysis and fatty acid oxidation fluxes in male mice, respectively. Furthermore, cardiac-specific knockdown phosphofructokinase-1, liver or overexpression long-chain acyl-CoA dehydrogenase partially rescues the cardiac hypertrophy in adult male KLF7 deficient mice. Here we show that the KLF7/PFKL/ACADL axis is a critical regulatory mechanism and may provide insight into viable therapeutic concepts aimed at the modulation of cardiac metabolic balance in hypertrophied and failing heart.

The relationship of superoxide dismutase and malondialdehyde levels with left ventricular geometry and function in patients with primary hypertension.

INTRODUCTION: To investigate the relationship of superoxide dismutase (SOD) and malondialdehyde (MDA) levels with left ventricular geometry (LVG) and function in patients with primary hypertension (PH). METHODS: A total of 222 PH patients and 25 healthy control (HC)s were enrolled in this study. All subjects underwent echocardiography and blood biochemical examination. PH patients were divided into four groups based on Ganau classification: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group, and concentric hypertrophy (CH) group. Pearson correlation analysis and logistic regression analysis were used to analyze the relationship between SOD and MDA with left ventricular structure and function. RESULTS: Compared to the HC, NG and CR groups, MDA level was higher while SOD level was lower in the EH and CH groups (all P < 0.001). SOD level was negatively correlated with IVSd, LVDd, LVPW, and global longitudinal strain (GLS), but positively correlated with LVEF. MDA level was positively correlated with IVSd, LVPW, and GLS, while negatively correlated with e'/a' and LVEF. SOD and MDA were independently associated with CR (OR = 0.970, P = 0.003; OR = 1.204, P = 0.043), EH (OR = 0.879, P < 0.001; OR = 2.197, P = 0.001) and CH (OR = 0.796, P < 0.001; OR = 3.669, P < 0.001). CONCLUSION: The SOD and MDA levels were correlated with LVG and function in PH patients. SOD and MDA may be important influencing factors of LVG change.

Sprayable NAHAO® hydrogel alleviates pain and accelerates rat oral mucositis wound healing.

OBJECTIVE: To investigate the promote healing and analgesic effects of NAHAO® Brand Nazhen oral antibacterial care solution (NAHAO® spray) on the 5-fluorouracil-induced oral mucositis in rats. MATERIAL AND METHOD: Sixty male SD rats were randomly divided into normal group, model group, recombinant human epidermal growth factor (rhEGF) group, NAHAO® spray group, and 1/3 concentration of NAHAO® spray group. 5-FU was injected intraperitoneally on the first and third days of the experimental model, and OM was induced using mechanical trauma on the third and fifth days. Wound healing quality was assessed by the appearance of mucosa and histological images on day6 and day10. Pain is measured by facial grooming behavior stimulated by capsaicin, the alternation of body weight and food intake was also recorded to reflect the OM pain. To examine the involvement of the cyclooxygenase pathway in the mechanism underlying oral mucositis, we detected the expression of cyclooxygenase2(COX-2) and matrix metalloproteinase 9(MMP9) via immunohistochemical staining and determined the PGE2 concentrations in rats' serum during healing of oral mucositis. RESULTS: NAHAO® spray attenuated pathological damage and reduced pain sensitivity effectively. COX-2 expression levels were inhibited in the NAHAO® spray-treated group. The concentration of PGE2 and the expression of MMP9 were inhibited in NAHAO®-treated rats. Compared with normal rats, the elevated rubbing time following capsaicin stimulation in the model was completely inhibited after being treated with NAHAO® spray. CONCLUSION: NAHAO® spray alleviated OM-induced pain and promoted wound healing partly by inhibiting the cyclooxygenase-related pathway.

A national survey on how to improve traditional Chinese medicine learning internationally: Perceptions from both teachers and students.

Background: With the increasing popularity of traditional Chinese medicine (TCM) by the global community, how to teach basic knowledge of TCM to international students and improve the teaching quality are important issues for teachers of TCM. The present study was to analyze the perceptions from both students and teachers on how to improve TCM learning internationally. Methods: A cross-sectional national survey was conducted at 23 universities/colleges across China. A structured, self-reported on-line questionnaire was administered to 34 Chinese teachers who taught TCM course in English and to 1016 international undergraduates who were enrolled in the TCM course in China between 2017 and 2021. Results: Thirty-three (97.1%) teachers and 900 (88.6%) undergraduates agreed Chinese culture should be fully integrated into TCM courses. All teachers and 944 (92.9%) undergraduates thought that TCM had important significance in the clinical practice. All teachers and 995 (97.9%) undergraduates agreed that modern research of TCM is valuable. Thirty-three (97.1%) teachers and 959 (94.4%) undergraduates thought comparing traditional medicine in different countries with TCM can help the students better understand TCM. Thirty-two (94.1%) teachers and 962 (94.7%) undergraduates agreed on the use of practical teaching method with case reports. From the perceptions of the undergraduates, the top three beneficial learning styles were practice (34.3%), teacher's lectures (32.5%), case studies (10.4%). The first choice of learning mode was attending to face-to-face teaching (82.3%). The top three interesting contents were acupuncture (75.5%), Chinese herbal medicine (63.8%), and massage (55.0%). Conclusion: To improve TCM learning among international undergraduates majoring in conventional medicine, integration of Chinese culture into TCM course, comparison of traditional medicine in different countries with TCM, application of the teaching method with case reports, and emphasization of clinical practice as well as modern research on TCM should be fully considered.

A novel nanoparticle system targeting damaged mitochondria for the treatment of Parkinson's disease.

Mitochondrial damage is one of the primary causes of neuronal cell death in Parkinson's disease (PD). In PD patients, the mitochondrial damage can be repaired or irreversible. Therefore, mitochondrial damage repair becomes a promising strategy for PD treatment. In this research, hyaluronic acid nanoparticles (HA-NPs) of different molecular weights are used to protect the mitochondria and salvage the mild and limited damage in mitochondria. The HA-NPs with 2190 k Dalton (kDa) HA can improve the mitochondrial function of SH-SY5Y cells and PTEN induced putative kinase 1 (PINK1) knockout mouse embryo fibroblast (MEF) cells. In cases of irreversible damage, NPs with ubiquitin specific peptidase 30 (USP30) siRNA are used to promote mitophagy. Meanwhile, by adding PINK1 antibodies, the NPs can selectively target the irreversibly damaged mitochondria, preventing the excessive clearance of healthy mitochondria.

The Effect of Group Identification on Death Anxiety: The Chain Mediation Role of Close Relationships and Self-Esteem.

Based on the terror management theory (TMT), this study integrated self-esteem and close relationships to explore the effects of group identification on death anxiety. Five hundred and four participants completed the Death Anxiety, Rosenberg Self-Esteem, Social Identity, and Inclusion of Other in the Self scales via online platforms. There were significant correlations among group identification, close relationship, self-esteem, and death anxiety. Group identification had a significant negative predictive effect on death anxiety. Specifically, group identification affects death anxiety through two pathways: the separate mediating role of self-esteem and the serial mediation pathway of close relationships → self-esteem. Our study provides direct evidence that group identification relieves death anxiety. The results showed that the alleviating function of group identification was mediated by self-esteem and close relationships. This study provides a new perspective concerning TMT as a defense mechanism against death anxiety.

Dysfunctional telomeres through mitostress-induced cGAS/STING activation to aggravate immune senescence and viral pneumonia.

Disproportionately high incidence and mortality of respiratory infection such as influenza A virus (IAV) and SARS-CoV-2 have been evidenced in the elderly, but the role and the mechanism of age-associated immune deregulation in disease exacerbation are not well defined. Using a late generation of mice deficient in telomerase RNA (Terc-/- ), we herein demonstrated that aged mice were exquisitely susceptible to respiratory viral infection, with excessive inflammation and increased mortality. Furthermore, we identified the cGAS/STING pathway, which was essentially induced by the leaked mitochondrial DNA, as a biologically relevant mechanism contributing to exaggerated inflammation in Terc-/- mice following viral infection. Innate immune cells, mainly, macrophages with shortened telomeres, exhibited hallmarks of cellular senescence, mitochondrial distress, and aberrant activation of STING and NLRP3 inflammasome pathways, which predisposed mice to severe viral pneumonia during commonly mild infections. Application of STING inhibitor and, more importantly, senolytic agent, reduced the burden of stressed macrophages, improved mitochondrial integrity, and suppressed STING activation, thereby conferring the protection for Terc-/- mice against respiratory infection. Together, the findings expand our understanding of innate immune senescence and reveal the potential of the senolytics as a promising treatment to alleviate the symptom of viral pneumonia, particularly for the older population.

Krüppel-like Transcription Factor 7 Is a Causal Gene in Autism Development.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disease. To date, more than 1000 genes have been shown to be associated with ASD, and only a few of these genes account for more than 1% of autism cases. Klf7 is an important transcription factor of cell proliferation and differentiation in the nervous system, but whether klf7 is involved in autism is unclear. METHODS: We first performed ChIP-seq analysis of klf7 in N2A cells, then performed behavioral tests and RNA-seq in klf7+/- mice, and finally restored mice with adeno-associated virus (AAV)-mediated overexpression of klf7 in klf7+/- mice. RESULTS: Klf7 targeted genes are enriched with ASD genes, and 631 ASD risk genes are also differentially expressed in klf7+/- mice which exhibited the core symptoms of ASD. When klf7 levels were increased in the central nervous system (CNS) in klf7+/- adult mice, deficits in social interaction, repetitive behavior and majority of dysregulated ASD genes were rescued in the adults, suggesting transcriptional regulation. Moreover, knockdown of klf7 in human brain organoids caused dysregulation of 517 ASD risk genes, 344 of which were shared with klf7+/- mice, including some high-confidence ASD genes. CONCLUSIONS: Our findings highlight a klf7 regulation of ASD genes and provide new insights into the pathogenesis of ASD and promising targets for further research on mechanisms and treatments.

A novel nano delivery system targeting different stages of osteoclasts.

Osteoclast (OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted delivery systems exist. Therefore, we designed two dual-targeting nanoparticles to target OCs at different functional stages. Using the calcitonin gene-related peptide receptor (CGRPR), which OC precursors highly express, and specific TRAPpeptides screened in the bone resorption lacuna, where mature OCs function, respectively, two types of dual-targeted nanoparticles were constructed. Afterwards, nanoparticles were grafted with hyaluronic acid (HA), which specifically binds to CD44 on the surface of the OCs. In vivo and in vitro experiments show that both nanoparticles have noticeable targeting effects on OCs. This suggests that dual-targeting nanoparticles designed for different functional periods of OC can be well targeted to the corresponding OC, and further promote the more precise delivery of drugs used to treat OP.

CERS6-AS1 promotes cell proliferation and represses cell apoptosis in pancreatic cancer via miR-195-5p/WIPI2 axis.

Pancreatic cancer (PC) is a lethal malignancy that threatens human health. Long noncoding RNAs (lncRNAs) act as important mediators in PC development. Our study aimed to investigate the function and mechanism of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) in PC. As shown by RT-qPCR, CERS6-AS1 was significantly upregulated in PC cells and tissues. Silencing CERS6-AS1 suppressed PC cell viability and proliferation while enhancing cell apoptosis according to colony formation assays, EdU assays, and flow cytometry analyses. Mechanistically, CERS6-AS1 interacted with miR-195-5p to elevate the expression level of the WD repeat domain phosphoinositide interacting 2 (WIPI2), which is a downstream target gene of miR-195-5p in PC. Moreover, miR-195-5p expression was negatively associated with CERS6-AS1 expression (or WIPI2 expression) in PC tissues. Rescue assays revealed that WIPI2 overexpression rescued the effects of CERS6-AS1 deficiency on cell viability, proliferation, and apoptosis. In summary, CERS6-AS1 facilitates PC cell proliferation while inhibiting PC cell apoptosis by upregulating WIPI2 via miR-195-5p. This study might provide promising insight into the role of CERS6-AS1 in PC development.

A Network Analysis of the Association Between Intergroup Contact and Intergroup Relations.

PURPOSE: Intergroup contact is an effective strategy to improve intergroup relationships. Although intergroup relationships have been studied extensively, the individual roles of quantity and quality of contact in relationships with cognition, emotion, and intention of behavior toward other ethnic minority groups are not fully understood. This study explores the situation via network analysis among Zhuang and Yao ethnic minorities in Southwest China. METHODS: We investigated the quantity and quality of intergroup contact and cognition, emotion, and intention of behavior among a sample of 543 Zhuang and 490 Yao ethnic group members. Data were analyzed using the R-package. Network structures were analyzed via the Qgraph package, and the accuracy and stability of the network were measured via the Bootnet package; communities were detected via the Igraph package; bridge analyses were conducted via the Networktools package; and the network difference was compared via the Network Comparison Test package. RESULTS: The results indicated perceived intimacy is the central node. Quantity of contact constructed a community with "perceived connection," "sense of community," "knowledge about out-group," and "perceived similarity." Meanwhile, quality of contact constructed a community with "intergroup attitude" and a "feeling thermometer." The remainder of the nodes constructed two additional communities. The network global connectivity and structure between the two ethnic groups were highly similar. CONCLUSION: The study examined the quantity and quality of intergroup contact via network analysis for two ethnic minority groups. It was shown that the two groups' global network structures of intergroup contact and their effects are highly similar. Specifically, quantity and quality of contact produce different effects on intergroup relations. Quantity of contact has proximal effects, including instant cognitive and emotional response without depth cognition, while quality of contact has proximal effects that may change deep-seated cognition and subsequently improve intergroup relations.

Anti-aging and anti-oxidant activities of murine short interspersed nuclear element antisense RNA.

Short interspersed nuclear elements (SINEs) play a key role in regulating gene expression, and SINE RNAs are involved in age-related diseases. We investigated the anti-aging effects of a genetically engineered murine SINE B1 antisense RNA (B1as RNA) and explored its mechanism of action in naturally senescent BALB/c (≥14 months) and moderately senscent C57BL/6N (≥9 months) mice. After tail vein injection, B1as RNA was available in the blood of mice for approximately 30 min, persisted for approximately 2-4 h in most detected tissues and persisted approximately 48 h in lungs. We found that treatment with B1as RNA improved stamina and promoted hair re-growth in aged mice. Treatment with B1as RNA also partially rescued the increase in mitochondrial DNA copy number in liver and spleen tissues observed in aged and moderately senescent mice. Finally, treatment with B1as RNA increased the activities of superoxide dismutase and glutathione peroxidase in aged and moderately senescent mice, reduced these animals' malondialdehyde and reactive oxygen species levels, and modulated the expression of several aging-associated genes, including Sirtuin 1, p21, p16Ink4a, p15Ink4b and p19Arf, and anti-oxidant genes (Sesn1 and Sesn 2). These data suggest that B1as RNA inhibits the aging process by enhancing antioxidant activity, promoting the scavenging of free radicals, and modulating the expression of aging-associated genes. This is the first report describing the anti-aging activity of SINE antisense RNA, which may serve as an effective nucleic acid drug for the treatment of age-related diseases.

The Ciji-Hua'ai-Baosheng II Formula Attenuates Chemotherapy-Induced Anorexia in Mice With H22 Hepatocellular Carcinoma.

Background: Ciji-Hua'ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medicine formula, which specifically targets different aspects of chemotherapy-induced adverse effects in patients with cancer. In our clinical application, CHB-II-F significantly alleviated chemotherapy-induced anorexia (loss of appetite) and improved the quality of life for patients with tumor during and after chemotherapy. However, the mechanism of CHB-II-F in alleviation of chemotherapy-induced anorexia remains to be further investigated. Aim of Study: To explore the therapeutic effect and mechanism of CHB-II-F on chemotherapy-induced anorexia in the mice model of H22 hepatoma. Materials and Methods: A total of 72 Kunming mice of SPF grade were inoculated subcutaneously with H22 hepatoma cells into the right anterior armpit of the mice. After 1 week of seeding, mice were injected intraperitoneally with a high dose of 5-fluorouracil (200 mg/kg 5-FU) to establish the model of chemotherapy. The mice were randomly divided into six groups: untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji capsule (YZXJC) group, and three groups of 5-FU plus different concentrations of CHB-II-F. All the mice in each group were treated for 14 days. The body weight, food intake, tumor volume, and tumor weight of mice were measured, and pathological examinations of tumor tissue, stomach, and duodenum were carried out. Expressions of serum Leptin, Neuropeptide Y (NPY), epidermal cell growth factor (EGF), Motilin (MTL), Orexin A (OXA), Gastrin (GAS), Ghrelin, Prostaglandin E2 (PGE2), and jejunum superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined. The protein and mRNA levels of proopiomelanocortin (POMC), Orexin receptor 1 (OX1R), neuropeptide Y (NPY), cocaine and amphetamine regulated transcript peptide (CART), Agouti gene-related protein (AgRP), Leptin receptor (Ob-R), and Ghrelin receptor (GHSR) were examined in hypothalamus, and the protein levels of substance P (SP) and 5-hydroxytryptamine (5-HT) in duodenum were measured. Results: The combination of CHB-II-F and 5-FU could enhance the inhibitory effect of 5-FU on tumor. The tumor inhibition rates of 5-FU group, YZXJC group, CHB-II-F(H) group, CHB-II-F(M) group, and CHB-II-F(L) group were 58.88, 28.08, 54.96, 37.69, and 28.61%, respectively. Compared with untreated group and 5-FU group, CHB-II-F significantly increased the body weight and food intake of tumor-bearing mice; increased the content of NPY, Orexin A, Ghrelin, GAS, MTL, EGF, and PGE2 in serum and the activity of SOD in jejunum; and decreased the content of Leptin in serum and the content of MDA in jejunum. Compared with untreated group and 5-FU group, CHB-II-F also enhanced the expression of OX1R, GHSR, NPY, and AgRP protein and gene and decreased the expression of Ob-R, POMC, and CART protein and gene in hypothalamus of mice, and the gene expression was consistent with the protein expression. In addition, CHB-II-F decreased the expression of 5-HT and SP protein in duodenum. Conclusion: In the murine model of H22 hepatocellular carcinoma (HCC) receiving chemotherapy, CHB-II-F enhances the inhibitory effect of 5-FU on tumor, significantly improves the pathological injury of gastrointestinal tract caused by chemotherapy, and regulates the secretion of gastrointestinal hormones. It may alleviate chemotherapy-induced anorexia by affecting appetite regulatory factors in the feeding area of hypothalamus central nervous system and peripheral appetite regulatory factors.