Effects of Music, Massage, Exercise, or Acupuncture in the Treatment of Depression Among College Students: A Network Meta-Analysis.

Objective: To assess the therapeutic impacts of exercise, massage, and music interventions on college students experiencing depression by employing a mesh meta-analysis approach. This research intends to offer valuable insights to aid in the development of non-pharmaceutical treatment strategies for depression. Methods: We conducted a thorough search across various databases including Cochrane, PubMed, Embase, Web of Science, CNKI, and Wanfang to explore the effects of music, massage, aerobic exercise, fitness Qigong, yoga, tai chi, ball games, strength training, dance, whole body vibration training, and high-intensity interval training on the treatment of depression in college students. The search period was from January 1, 2023, which marks the establishment of each database. Subsequently, a mesh meta-analysis was performed using the "Stata 15.1" software, incorporating outcome indicators from 24 included literature comprising a total of 1458 patients. Results: Based on the ranking of the optimal intervention effects of various non-pharmaceutical methods, the order, from highest to lowest probability, was as follows: high-intensity interval training (96%), yoga (94.90%), dance (78.30%), music (73.30%), ball games (62.50%), strength training (51.70%), aerobic training (45.30%), tai chi (35.40%), vibration training (27.30%), massage (20.10%), qigong (14.30%), and no intervention (1.00%). This ranking aligns closely with the findings obtained from pairwise comparisons between different interventions. Conclusion: High-intensity interval training is likely to yield the most effective therapeutic results for college students with depression. In the pairwise comparison of different interventions, High-intensity interval training is also better than most interventions. However, to establish its intervention effect more conclusively, further validation through additional high-quality randomized controlled trials is necessary.

Endogenously decreasing tissue n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apolipoprotein E-deficient mice by inhibiting systemic and vascular inflammation.

OBJECTIVE: To use the fat-1 transgenic mouse model to determine the role of tissue n-6/n-3 fatty acid ratio in atherosclerotic plaque formation. Although it has been suggested that a low ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) is more desirable in reducing the risk of atherosclerotic cardiovascular disease, the role of tissue n-6/n-3 fatty acid ratio in atherosclerosis has not been sufficiently tested in a well-controlled experimental system. The fat-1 transgenic mouse model, expressing an n-3 fatty acid desaturase, is capable of producing n-3 PUFAs from n-6 PUFAs and thereby has a ratio of n-6/n-3 fatty acids close to 1:1 in tissues and organs. METHODS AND RESULTS: To generate apolipoprotein E-deficient plus fat-1 transgenic mice (apoE(-/-)/fat-1), we crossed heterozygous fat-1 mice with apoE(-/-) mice. After 14 weeks of a Western-type diet rich in n-6 PUFAs, the apoE(-/-)/fat-1 mice showed a lower ratio of n-6/n-3 fatty acids than the apoE(-/-) mice in all organs and tissues tested. The aortic lesion area in apoE(-/-)/fat-1 mice was significantly reduced when compared with that of apoE(-/-) littermates (7.14±0.54% versus 13.49±1.61%). There were no differences in plasma cholesterol or high- and low-density lipoprotein levels between the 2 groups, except for a higher triglyceride level in the apoE(-/-)/fat-1 mice. A significant reduction of interleukin 6 and prostaglandin E(2) in both plasma and aorta culture medium was observed in apoE(-/-)/fat-1 mice. RT-PCR analysis also indicated that the expression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, interleukin 6, and cyclooxygenase-2 was lower in the aortas and the circulating monocytes from apoE(-/-)/fat-1 mice. In addition, the expression of nuclear factor κB/p65 in the aorta and the recruitment of macrophages into atherosclerotic plaques were reduced in apoE(-/-)/fat-1 mice, compared with apoE(-/-) mice. CONCLUSIONS: To our knowledge, this is the first study to provide direct evidence for the role of tissue n-6/n-3 ratio in atherosclerosis using the fat-1 transgenic mouse model. Our findings demonstrate that a decreased n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apoE(-/-) mice. This protective effect may be attributed to the antiinflammatory properties of n-3 fatty acids, rather than their lipid-lowering effect.

Panax notoginseng reduces atherosclerotic lesions in ApoE-deficient mice and inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion.

It is widely recognized that atherogenesis is associated with vascular inflammation. Panax notoginseng , a commonly used herb in China, has been shown to possess anti-inflammatory activity. In the present study, the antiatherogenic effect of P. notoginseng saponins (PNS) was examined in apolipoprotein E (apoE)-deficient mice. The molecular mechanisms responsible for the antivascular inflammatory effect of PNS on human coronary artery endothelial cells (HCAECs) were also investigated in vitro. PNS, dissolved in drinking water, was administered orally to two treatment groups at dosages of 4.0 and 12.0 mg/day/mouse, respectively. After 8 weeks, atherosclerosis in the entire aortic area was assessed using an en face method. Compared with the control group, both low- and high-dose PNS-treated groups showed a significant decrease in extent of atherosclerotic lesions by 61.4 and 66.2%, respectively (P < 0.01). PNS also notably reduced serum lipid levels. Serum levels of IL-6 and TNF-alpha in all groups of apoE-deficient mice were below the detection limit. In vitro studies showed that PNS dose-dependently inhibited monocyte adhesion on activated endothelium, as well as the expression of TNF-alpha-induced endothelial adhesion molecules, such as ICAM-1 and VCAM-1. In conclusion, PNS has antiatherogenic activity through, at least in part, its lipid-lowering and antivascular inflammatory mechanisms.

Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid.

Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LC-PUFA), highly enriched in the central nervous system, is critical for brain development and function. It has been shown that DHA deficiency impairs cognitive performance whereas DHA supplementation improves the condition. However, the mechanisms underlying the role of DHA in brain development and function remain to be elucidated. By using transgenic fat-1 mice rich in endogenous n-3 PUFA, we show that increased brain DHA significantly enhances hippocampal neurogenesis shown by an increased number of proliferating neurons and neuritogenesis, evidenced by increased density of dendritic spines of CA1 pyramidal neurons in the hippocampus. Concurrently, fat-1 mice exhibit a better spatial learning performance in the Morris water maze compared with control WT littermates. In vitro experiments further demonstrate that DHA promotes differentiation and neurite outgrowth of neuronal cells derived from mouse ES cells and increases the proliferation of cells undergoing differentiation into neuronal lineages from the ES cells. These results together provide direct evidence for a promoting effect of DHA on neurogenesis and neuritogenesis and suggest that this effect may be a mechanism underlying its beneficial effect on behavioral performance.

Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells.

Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment, but the efficacy and drug resistance remain to be clinical concerns. The purpose of this study was to determine whether the extracts of coptis, an anti-inflammatory herb, improve the anticancer efficacy of ER antagonists. The results showed that the combined treatment of ER antagonists and the crude extract of coptis or its purified compound berberine conferred synergistic growth inhibitory effect on MCF-7 cells (ER+), but not on MDA-MB-231 cells (ER-). Similar results were observed in the combined treatment of fulvestrant, a specific aromatase antagonist. Analysis of the expression of breast cancer related genes indicated that EGFR, HER2, bcl-2, and COX-2 were significantly downregulated, while IFN-beta and p21 were remarkably upregulated by berberine. Our results suggest that coptis extracts could be promising adjuvant to ER antagonists in ER positive breast cancer treatment through regulating expression of multiple genes.

Reduction of inflammation and chronic tissue damage by omega-3 fatty acids in fat-1 transgenic mice with pancreatitis.

Pancreatitis is a severe debilitating disease with high morbidity and mortality. Treatment is mostly supportive, and until now there are no clinically useful strategies for anti-inflammatory therapy. Although omega-3 polyunsaturated fatty acids (n-3 PUFA) are known to have anti-inflammatory effects, the utility of these fatty acids in the alleviation of pancreatitis remained to be investigated. The aim of this study was to examine the effect of n-3 PUFA on both acute and chronic pancreatitis in a well-controlled experimental system. We used the fat-1 transgenic mouse model, characterized by endogenously increased tissue levels of n-3 PUFA, and their wild-type littermates to examine the effect of n-3 PUFA on both acute and chronic cerulein-induced pancreatitis. Disease activity and inflammatory status were assessed by both histology and molecular methods. In acute pancreatitis, fat-1 mice showed a trend towards decreased necrosis and significantly reduced levels of plasma IL-6 levels as well as reduced neutrophil infiltration in the lung. In chronic pancreatitis there was less pancreatic fibrosis and collagen content accompanied by decreased pancreatic stellate cell activation in the fat-1 animals with increased n-3 PUFA tissue levels as compared to wild-type littermates with high levels of omega-6 (n-6) PUFA in their tissues. Our data provide evidence for a reduction of systemic inflammation in acute pancreatitis and of tissue fibrosis in chronic pancreatitis by increasing the tissue content of omega-3 polyunsaturated fatty acids. These results suggest a beneficial potential for n-3 PUFA supplementation in acute and particularly chronic pancreatitis.

Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids.

Colorectal cancer (CRC) is the second leading cause of cancer deaths in USA. Anti-inflammatory drugs were shown to be effective in the prevention of CRC, supporting a link between inflammation and tumorigenesis in the colon. However, due to their side effects, long-term administration of these drugs for CRC prevention is not feasible. An increased tissue content of omega-3 polyunsaturated fatty acids (n-3 PUFA) can dampen colon inflammation in animals as well as in humans. Whether increasing colon tissue n-3 PUFA alone is effective in preventing colon tumorigenesis remains to be investigated. Here we show that endogenously increased tissue levels of n-3 PUFA in the fat-1 transgenic mouse model lower incidence and growth rate of colon tumors induced by inflammation (dextrane sodium sulfate) plus treatment with carcinogen (azoxymethane). This was accompanied by lower activity of nuclear factor kappa B (NF-kappaB), higher expression of transforming growth factor beta in the colons and lower expression of inducible nitric oxide synthase in the tumors of fat-1 animals. Our data provide new insight into the mechanism by which n-3 PUFA suppresses tumorigenesis through dampening of inflammation and NF-kappaB activity. These results support a protective role of n-3 PUFA supplementation in the prevention of CRC.

Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids.

The protective effect of early pregnancy against breast cancer can be attributed to the transition from undifferentiated cells in the nulliparous to the differentiated mature cells during pregnancy. Considerable evidence suggests strongly that the n-3 polyunsaturated fatty acid (PUFA) content of adipose breast tissue is inversely associated with an increased risk of breast cancer. Here, we report that there was a decrease in the n-6/n-3 PUFA ratio and a significant increase in concentration of n-3 PUFA docosapentaenoic acid and eicosapentaenoic acid in the pregnant gland. The functional role of n-3 PUFAs on differentiation was supported by the studies in the fat-1 transgenic mouse, which converts endogenous n-6 to n-3 PUFAs. Alternation of the n-6/n-3 ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid, in the mammary gland of fat-1 mouse resulted in development of lobulo-alveolar-like structure and milk protein beta-casein expression, mimicking the differentiated state of the pregnant gland. Docosapentaenoic acid and eicosapentaenoic acid activated the Jak2/Stat5 signaling pathway and induced a functional differentiation with production of beta-casein. Expression of brain type fatty acid binding protein brain type fatty acid binding protein in virgin transgenic mice also resulted in a reduced ratio of n-6/n-3 PUFA, a robust increase in docosapentaenoic acid accumulation, and mammary differentiation. These data indicate a role of mammary derived growth inhibitor related gene for preferential accumulation of n-3 docosapentaenoic acid and eicosapentaenoic acid in the differentiated gland during pregnancy. Thus, alternation of n-6/n-3 fatty acid compositional ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid and eicosapentaenoic acid, is one of the underlying mechanisms of pregnancy-induced mammary differentiation.

Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines.

UNLABELLED: Cytokines such as tumor necrosis factor alpha (TNF-alpha) are key factors in liver inflammation. Supplementation with essential omega-3 polyunsaturated fatty acids (n-3 PUFA) has been demonstrated to lower TNF-alpha and IL-1 production in mononuclear cells. An inflammation-dampening effect has been observed with increased omega-3 fatty acid supplementation in several inflammatory diseases. In this study, we used the transgenic fat-1 mouse, expressing a Caenorhabditis elegans desaturase endogenously forming n-3 PUFA from n-6 PUFA, to analyze the effect of an increased n-3 PUFA tissue status in the macrophage-dependent acute D-galactosamine/lipopolysaccaride (D-GalN/LPS) hepatitis model. We show less severe inflammatory liver injury in fat-1 mice with a balanced n-6/n-3 PUFA ratio as evidenced by reduced serum alanine aminotransferase levels and less severe histological liver damage. This decreased inflammatory response was associated with decreased plasma TNF-alpha levels and with reduced hepatic gene expression of TNF-alpha, IL-1beta, IFN-gamma and IL-6 in fat-1 mice, leading to a decreased rate of apoptosis in livers from fat-1 animals, as measured by DAPI-staining. CONCLUSION: The results of this study offer evidence for an inflammation dampening effect of omega-3 polyunsaturated fatty acids in the context of liver inflammation.

Melanoma growth is reduced in fat-1 transgenic mice: impact of omega-6/omega-3 essential fatty acids.

An important nutritional question as to whether the ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids plays a role in tumorigenesis remains to be clarified in well qualified experimental models. The recently engineered fat-1 mice, which can convert n-6 to n-3 fatty acids and have a balanced ratio of n-6 to n-3 fatty acids in their tissues and organs independent of diet, allow carefully controlled studies to be performed in the absence of potential confounding factors of diet and therefore are a useful model for elucidating the role of n-6/n-3 fatty acid ratio in tumorigenesis. We implanted mouse melanoma B16 cells into transgenic and WT littermates and examined the incidence of tumor formation and tumor growth rate. The results showed a dramatic reduction of melanoma formation and growth in fat-1 transgenic mice. The level of n-3 fatty acids and their metabolite prostaglandin E(3) (PGE(3)) were much higher (but the n-6/n-3 ratio is much lower) in the tumor and surrounding tissues of fat-1 mice than that of WT animals. The phosphatase and tensin homologue deleted on the chromosome 10 (PTEN) gene was significantly up-regulated in the fat-1 mice. In vitro experiments showed that addition of the n-3 fatty acid eicosapentaenoic acid or PGE(3) inhibited the growth of B16 cell line and increased the expression of PTEN, which could be partially attenuated by inhibition of PGE(3) production, suggesting that PGE(3) may act as an antitumor mediator. These data demonstrate an anticancer (antimelanoma) effect of n-3 fatty acids through, at least in part, activation of PTEN pathway mediated by PGE(3).

Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis.

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are the precursors of potent lipid mediators and play an important role in regulation of inflammation. Generally, n-6 PUFA promote inflammation whereas n-3 PUFA have antiinflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived proinflammatory eicosanoids. Newly discovered resolvins and protectins are potent antiinflammatory lipid mediators derived directly from n-3 PUFA with distinct pathways of action. However, the role of the n-3 PUFA tissue status in the formation of these antiinflammatory mediators has not been addressed. Here we show that an increased n-3 PUFA tissue status in transgenic mice that endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant formation of antiinflammatory resolvins and effective reduction in inflammation and tissue injury in colitis. The endogenous increase in n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid mediators such as leukotriene B4 and prostaglandin E2. The observed inflammation protection might result from decreased NF-kappaB activity and expression of TNFalpha, inducible NO synthase, and IL-1beta, with enhanced mucoprotection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish the fat-1 transgenic mouse as a new experimental model for the study of n-3 PUFA-derived lipid mediators. They add insight into the molecular mechanisms of inflammation protection afforded by n-3 PUFA through formation of resolvins and protectins other than inhibition of n-6 PUFA-derived eicosanoid formation.

The extract of huanglian, a medicinal herb, induces cell growth arrest and apoptosis by upregulation of interferon-beta and TNF-alpha in human breast cancer cells.

Huanglian (Coptidis rhizoma), a widely used herb in traditional Chinese medicine, has been shown recently to possess anticancer activities. However, the molecular mechanism underlying the anticancer effect of the herb is poorly understood. Specifically, whether huanglian extract affects the expression of cancer-related genes has not been defined. This study used DNA microarray technology to examine the effect of the herbal extract on expression of the common genes involved in carcinogenesis in two human breast cancer cell lines, the ER-positive MCF-7 and ER-negative MDA-MB-231 cells. Treatment of the cancer cells with huanglian extract markedly inhibited their proliferation in a dose- and time-dependent manner. The growth inhibitory effect was much more profound in MCF-7 cell line than that in MDA-MB-231 cells. DNA microarray assay revealed that treatment with huanglian dramatically increased the mRNA expression of interferon-beta (IFN-beta) and tumor necrosis factor-alpha in MCF-7 cells. Quantitative analysis by real-time PCR or western blotting confirmed the upregulation of the two genes (especially IFN-beta) in MCF-7 cells, but not in MDA-MB-231 cells. Addition of neutralizing antibody against IFN-beta to culture medium markedly inhibited the huanglian-induced antiproliferative effect, confirming the involvement of IFN-beta in the huanglian's effect and also suggesting an autocrine pathway for the action of IFN-beta in this setting. Given that IFN-beta is among the most important anticancer cytokines, the upregulation of this gene by huanglian is, at least in part, responsible for its antiproliferative effect. The results of this study implicate huanglian as a promising herb for chemoprevention and chemotherapy of certain cancers.

Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes.

Recent studies have shown opposing effects of n-6 and n-3 fatty acids on the development of cancer and suggest a role for the ratio of n-6 to n-3 fatty acids in the control of cancer. However, whether an alteration in the n-6/n-3 fatty acid ratio of cancer cells affects their invasive potential has not been well investigated. We recently developed a genetic approach to modify the n-6/n-3 ratio by expression of the Caenorhabditis elegans fat-1 gene encoding an n-3 desaturase that converts n-6 to n-3 fatty acids in mammalian cells. The objective of this study was to examine the effect of alteration in the n-6/n-3 fatty acid ratio on the invasive potential of human lung cancer A549 cells. Adenovirus-mediated gene transfer of the n-3 desaturase resulted in a marked reduction of the n-6/n-3 fatty acid ratio, particularly the ratio of arachidonic acid to eicosapentaenic acid. Cell adhesion assay showed that the cells expressing fat-1 gene had a delayed adhesion and retarded colonization. Matrigel assay for invasion potential indicated a 2-fold reduction of cell migration in the fat-1 transgenic cells when compared with the control cells. An increased apoptosis was also observed in the fat-1 transgenic cells. Microarray and quantitative polymerase chain reaction revealed a downregulation of several adhesion/invasion-related genes (MMP-1, integrin-alpha2 and nm23-H4) in the fat-1 transgenic cells. These results demonstrate that a decreased n-6/n-3 fatty acid ratio reduces the invasion potential of human lung cancer cells by probably downregulating the cell adhesion/invasion-related molecules, suggesting a role for the ratio of n-6 to n-3 fatty acids in the prevention and treatment of cancer.

Transgenic mice: fat-1 mice convert n-6 to n-3 fatty acids.

Mammals cannot naturally produce omega-3 (n-3) fatty acids--beneficial nutrients found mainly in fish oil--from the more abundant omega-6 (n-6) fatty acids and so they must rely on a dietary supply. Here we show that mice engineered to carry a fat-1 gene from the roundworm Caenorhabditis elegans can add a double bond into an unsaturated fatty-acid hydrocarbon chain and convert n-6 to n-3 fatty acids. This results in an abundance of n-3 and a reduction in n-6 fatty acids in the organs and tissues of these mice, in the absence of dietary n-3. As well as presenting an opportunity to investigate the roles played by n-3 fatty acids in the body, our discovery indicates that this technology might be adapted to enrich n-3 fatty acids in animal products such as meat, milk and eggs.