IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation.

Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.

14-3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer.

Over the past decade, the role of the 14-3-3 protein has received increasing interest. Seven subtypes of 14-3-3 proteins exhibit high homology; however, each subtype maintains its specificity. The 14-3-3ε protein is involved in various physiological processes, including signal transduction, cell proliferation, apoptosis, autophagy, cell cycle regulation, repolarization of cardiac action, cardiac development, intracellular electrolyte homeostasis, neurodevelopment, and innate immunity. It also plays a significant role in the development and progression of various diseases, such as cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancer. These immense and various involvements of 14-3-3ε in diverse processes makes it a promising target for drug development. Although extensive research has been conducted on 14-3-3 dimers, studies on 14-3-3 monomers are limited. This review aimed to provide an overview of recent reports on the molecular mechanisms involved in the regulation of binding partners by 14-3-3ε, focusing on issues that could help advance the frontiers of this field. Video Abstract.

KOtBu-Promoted, Three-Component Domino Reaction of Arenes(indoles/phenols), C60, and (Per/poly)fluoroarenes: Achieving Direct C-C Cross-Coupling of Fullerene with (Per/poly)fluoroarenes.

A KOtBu-promoted, three-component cross-coupling of arenes(indoles/phenols), C60, and (per/poly)fluoroarenes has been established for the one-pot efficient synthesis of various 1,4-arene-bridged bis(polyfluoroaryl)-functionalized [60]fullerenes. This developed reaction system demonstrates good functional group compatibilities with broad substrate scope, which exhibits high regio- and chemoselectivities. Further control experiment succeeded in providing a one-pot protocol for the synthesis of various 1,2-N-(per/poly)fluoroarene-substituted 1,2-(3-indole)(hydro)fullerenes.

Berberine-Based Carbon Quantum Dots Improve Intestinal Barrier Injury and Alleviate Oxidative Stress in C57BL/6 Mice with 5-Fluorouracil-Induced Intestinal Mucositis by Enhancing Gut-Derived Short-Chain Fatty Acids Contents.

This study aims to evaluate the effect of berberine-based carbon quantum dots (Ber-CDs) on improving 5-fluorouracil (5-FU)-induced intestinal mucositis in C57BL/6 mice, and explored the mechanisms behind this effect. Thirty-two C57BL/6 mice were divided into four groups: normal control (NC), 5-FU-induced intestinal mucositis model (5-FU), 5-FU + Ber-CDs intervention (Ber-CDs), and 5-FU + native berberine intervention (Con-CDs). The Ber-CDs improved body weight loss in 5-FU-induced mice with intestinal mucositis compared to the 5-FU group. The expressions of IL-1ß and NLRP3 in spleen and serum in Ber-CDs and Con-Ber groups were significantly lower than those in the 5-FU group, and the decrease was more significant in the Ber-CDs group. The expressions of IgA and IL-10 in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, but the up-regulation was more significant in the Ber-CDs group. Compared with the 5-FU group, the relative contents of Bifidobacterium, Lactobacillus and the three main SCFAs in the colon contents were significantly increased the Ber-CDs and Con-Ber groups. Compared with the Con-Ber group, the concentrations of the three main short-chain fatty acids in the Ber-CDs group were significantly increased. The expressions of Occludin and ZO-1 in intestinal mucosa in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, and the expressions of Occludin and ZO-1 in the Ber-CDs group were more higher than that in the Con-Ber group. In addition, compared with the 5-FU group, the damage of intestinal mucosa tissue in the Ber-CDs and Con-Ber groups were recovered. In conclusion, berberine can attenuate intestinal barrier injury and oxidative stress in mice to mitigate 5-fluorouracil-induced intestinal mucositis, moreover, the above effects of Ber-CDs were more significant than those of native berberine. These results suggest that Ber-CDs may be a highly effective substitute for natural berberine.

Lactiplantibacillus plantarum NKK20 Alleviates High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease in Mice through Regulating Bile Acid Anabolism.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.

Integrated regulation of chondrogenic differentiation in mesenchymal stem cells and differentiation of cancer cells.

Chondrogenesis is the formation of chondrocytes and cartilage tissues and starts with mesenchymal stem cell (MSC) recruitment and migration, condensation of progenitors, chondrocyte differentiation, and maturation. The chondrogenic differentiation of MSCs depends on co-regulation of many exogenous and endogenous factors including specific microenvironmental signals, non-coding RNAs, physical factors existed in culture condition, etc. Cancer stem cells (CSCs) exhibit self-renewal capacity, pluripotency and cellular plasticity, which have the potential to differentiate into post-mitotic and benign cells. Accumulating evidence has shown that CSCs can be induced to differentiate into various benign cells including adipocytes, fibrocytes, osteoblast, and so on. Retinoic acid has been widely used in the treatment of acute promyelocytic leukemia. Previous study confirmed that polyploid giant cancer cells, a type of cancer stem-like cells, could differentiate into adipocytes, osteocytes, and chondrocytes. In this review, we will summarize signaling pathways and cytokines in chondrogenic differentiation of MSCs. Understanding the molecular mechanism of chondrogenic differentiation of CSCs and cancer cells may provide new strategies for cancer treatment.

Short-Chain Fatty Acids Weaken Ox-LDL-Induced Cell Inflammatory Injury by Inhibiting the NLRP3/Caspase-1 Pathway and Affecting Cellular Metabolism in THP-1 Cells.

Short-chain fatty acids (SCFAs) are important anti-inflammatory metabolites of intestinal flora. Oxidized low-density lipoprotein (ox-LDL)-induced macrophage activation is critical for the formation of atherosclerosis plaque. However, the association between SCFAs and ox-LDL-induced macrophage activation with respect to the formation of atherosclerosis plaque has not yet been elucidated. The present study investigated whether SCFAs (sodium acetate, sodium propionate, and sodium butyrate) can affect ox-LDL-induced macrophage activation and potential signaling pathways via regulation of the expression of the NLRP3/Caspase-1 pathway. Using human monocyte-macrophage (THP-1) cells as a model system, it was observed that ox-LDL not only induced cell inflammatory injury but also activated the NLRP3/Caspase-1 pathway. The exogenous supplementation of three SCFAs could significantly inhibit cell inflammatory injury induced by ox-LDL. Moreover, three SCFAs decreased the expression of IL-1ß and TNF-α via the inactivation of the NLRP3/Caspase-1 pathway induced by ox-LDL. Furthermore, three SCFAs affected cellular metabolism in ox-LDL-induced macrophages, as detected by untargeted metabolomics analysis. The results of the present study indicated that three SCFAs inhibited ox-LDL-induced cell inflammatory injury by blocking the NLRP3/Caspase-1 pathway, thereby improving cellular metabolism. These findings may provide novel insights into the role of SCFA intervention in the progression of atherosclerotic plaque formation.

Sodium Butyrate Attenuates AGEs-Induced Oxidative Stress and Inflammation by Inhibiting Autophagy and Affecting Cellular Metabolism in THP-1 Cells.

In recent years, sodium butyrate has gained increased attention for its numerous beneficial properties. However, whether sodium butyrate could alleviate inflammatory damage by macrophage activation and its underlying mechanism remains unclear. The present study used an advanced glycosylation products- (AGEs-) induced inflammatory damage model to study whether sodium butyrate could alleviate oxidative stress, inflammation, and metabolic dysfunction of human monocyte-macrophage originated THP-1 cells in a PI3K-dependent autophagy pathway. The results indicated that sodium butyrate alleviated the AGEs-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased malondialdehyde (MDA) and mRNA expression of pro-inflammatory cytokines of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and increased the content of superoxide dismutase (SOD). Sodium butyrate reduced the protein expression of the NLR family, pyrin domain-containing protein 3 (NLRP3) and Caspase-1, and decreased the nucleus expression of nuclear factor-kappaB (NF-κB). Sodium butyrate decreased the expression of light-chain-associated protein B (LC3B) and Beclin-1, and inhibited autophagy. Moreover, sodium butyrate inhibited the activation of the PI3K/Akt pathway in AGEs-induced THP-1 cells. In addition, the metabolomics analysis showed that sodium butyrate could affect the production of phosphatidylcholine, L-glutamic acid, UDP-N-acetylmuraminate, biotinyl-5'-AMP, and other metabolites. In summary, these results revealed that sodium butyrate inhibited autophagy and NLRP3 inflammasome activation by blocking the PI3K/Akt/NF-κB pathway, thereby alleviating oxidative stress, inflammation, and metabolic disorder induced by AGEs.

Evaluation of Induced Apoptosis by Biosynthesized Zinc Oxide Nanoparticles in MCF-7 Breast Cancer Cells Using Bak1 and Bclx Expression.

Zinc oxide nanoparticles (ZnO NPs) have peaked interests in many researches in these recent years due to their advantageous application in modern health care applications. Therefore, we successfully synthesized ZnO NPs by Acacia luciana flower extract as stabilizing, reducing and capping agent, to investigate the antiproliferative potential and apoptosis induction in breast cancer cell lines. The involvements of Acacia luciana bioactive compounds in the stabilization of the ZnO NPs were confirmed by FTIR analysis. FESEM and EDS instruments confirmed that biosynthesized nanoparticles have an irregular morphology and mostly composed of Zn, C, and O respectively. The TEM and zeta potential instruments confirmed that biosynthesized nanoparticles have slight negative charges with particle size of 40 nm. The survivorship of MCF-7 cells were examined by MTT assay and revealed that ZnO NPs inhibited cell viability in a dose- and time-dependent effect with IC50 value of 3.1 µg/mL after 72 h exposure. Also, as a novel work onto ZnO NPs obtained by Acacia extracts, the Bak1/Bclx expression ratio was elucidated utilizing RT-PCR technique. The results demonstrated that ZnO NPs could enhance the expression ratio; therefore they have the potential to induce apoptosis in breast cancer cells via mitochondria-mediated apoptotic pathway.

Polarization-maintained propagation of a 2200 µm2 effective-area higher-order-mode in a bent optical fiber.

We report on the excitation and polarization preserved propagation of a very large effective-area (Aeff ∼ 2240 µm2) higher-order-mode in an optical fiber. A laser signal operating in the 1 µm wavelength region is transported in a Bessel-like LP0,4 mode over a 10 m long section of the polarization-maintaining higher-order-mode fiber. We observe that the light propagates through the fiber with >10 dB polarization-extinction-ratio as the fiber is coiled into circular loops of 40 cm diameter.

Rapamycin ameliorates immune-mediated aplastic anemia by inhibiting the proliferation and metabolism of T cells.

Aplastic anemia (AA) is a serious blood system disease that threatens human health. At present, the main cause of this disease is believed to be immune hyperfunction. However, the specific metabolic mode involved in the occurrence of lymphocytes in AA is still unknown. In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. We induced an AA mouse model through the classical immune-mediated pathway and simultaneously administered rapamycin intervention therapy. First, the AA-associated phenotypic changes and the efficacy of rapamycin in the treatment of AA were discussed. Second, the proliferation and metabolic pathway of bone marrow (BM) lymphocytes in AA and the effect of rapamycin on this process were determined. Finally, the expression levels of mTOR pathway-related proteins were analyzed. By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Moreover, we found that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and that rapamycin can inhibit this process. We confirmed that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. This viewpoint may provide a new therapeutic idea for clinical applications.

LGR6 promotes osteogenesis by activating the Wnt/ß-catenin signaling pathway.

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a member of the rhodopsin-like 7-transmembrane domain receptor superfamily and has high homology to LGR4 and LGR5. LGR6 is highly expressed in osteoblastic progenitors, and LGR6-deficient mice show nail and bone regeneration defect. However, the effect of LGR6 on the osteogenic differentiation of osteoblastic progenitors and its underlying mechanisms are largely unknown. In this study, we overexpressed and knockdown LGR6 with lentivirus in the preosteoblastic cell MC3T3-E1 to observe the effect of LGR6 on osteogenic differentiation and explore its possible molecular mechanism. LGR6 overexpression promoted osteogenic differentiation and mineralization by stabilizing ß-catenin to potentiate the Wnt/ß-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing ß-catenin degradation to inactivate the Wnt/ß-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing ß-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation.

[Shensong Yangxin Capsules in the adjuvant treatment of stable angina pectoris:a Meta-analysis and trial sequential analysis].

To systemically evaluate the benefits and side effects of Shensong Yangxin Capsules( SYC) in the adjuvant treatment of stable angina pectoris( SAP). Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP,Wan Fang database) were retrieved to collect the randomized controlled trials( RCTs) about therapeutic efficacy of SYC combined with routine drug( trial group) vs routine drug( control group) in the treatment of SAP. The methodological quality of the RCTs was evaluated based on the cochrane risk of bias assessment tool. The data were extracted and Meta-analyzed by Reviewer Manager 5. 3. TSA 0. 9 software was used for trial sequential analysis( TSA) of the total effective rate of symptoms improvement. A total of 15 RCTs with 1 316 participants were included. RESULTS:: of Meta-analysis showed that the total effective rate of angina symptoms improvement( RR = 1. 15,95% CI[1. 09,1. 21],P<0. 001) of trial group were significantly higher than those of control group,with statistical significance,the total effective rate of electrocardiograms( ECG) improvement( RR = 1. 10,95% CI[0. 94,1. 29],P = 0. 25) of trial group were significantly higher than those of control group,but the difference was not statistically significant. After treatment,the improvement of the total time of 24 h general ischemia( SMD =-1. 21,95%CI[-1. 97,-0. 45],P = 0. 002),the ST-segment depression amplitude( SMD =-1. 30,95%CI [-1. 52,-1. 09],P<0. 001),the duration of angina pectoris attack( SMD =-1. 16,95% CI[-1. 36,-0. 95],P< 0. 001),the angina pectoris attack every week( SMD =-0. 80,95%CI[-1. 10,-0. 50],P<0. 001),the onsumption of nitroglycerin every week( SMD=-0. 72,95%CI[-1. 05,-0. 39],P<0. 001) in the trial group were better than that of the control group,and the difference was statistically significant. Besides,the improvement of the blood lipid and high sensitivity C reactive protein( hs-CRP) in the trial group were better than those of the control group after treatment,and the difference was statistically significant( P< 0. 001). Funnel plots and Egger's linear regression showed that there was no publication bias. By sensitivity analysis,it showed that the results of this study were stable and reliable. No obvious adverse drug reactions were observed in all studies. TSA analysis showed that the evidence of Meta-analysis was reliable. SYC combined with routine Western medicine treatment for SAP can improve the total effective rate of angina pectoris,reduce 24 h total ischemia time,ST segment depression amplitude,duration of angina pectoris attack,frequency of angina pectoris attack and nitroglycerin dosage,and also can improve blood lipid and hs-CRP levels.

Polarization-maintaining, large-effective-area, higher-order-mode fiber.

Higher-order-mode (HOM) fibers guiding light in large-effective-area (Aeff) Bessel-like modes have recently generated great interest for high-power laser applications. A polarization-maintaining (PM) version of HOM fibers can afford the added possibility of coherent beam combination, improved material processing, and polarization multiplexing of high-power fiber lasers. We report a PM-HOM fiber for guiding Bessel-like modes with Aeff ranging from 1200-2800 µm2. The fiber modes exhibit a birefringence value that compares well with that of a conventional single-mode PM fiber (2×10-4), and exhibit a polarization extinction ratio ranging from 13-23 dB over meter-long fiber lengths, practical for amplifier systems. This fiber presents a unique platform for next-generation high-power fiber systems, as well as for the fundamental studies on deterministically polarized Bessel-like modes in fibers.

High-power broadband Yb-free clad-pumped EDFA for L-band DWDM applications.

We demonstrated high-power broadband Yb-free clad-pumped erbium-doped fiber amplifier (EDFA) using commercial available low-cost 976 nm multimode diodes. An output power +33 dBm with less than ±1 dB natural gain flatness over a gain bandwidth of 33 nm (1570.3-1603.3 nm) was obtained using a new double-clad erbium-doped fiber which has a large core diameter of 17 µm and low NA of 0.11. The saturated output power, net gain, noise figure, and optical power conversion efficiency of the clad-pumped EDFA were characterized, and system impact of LP11 mode and four-wave-mixing nonlinearity were also evaluated.

Seven-core erbium-doped double-clad fiber amplifier pumped simultaneously by side-coupled multimode fiber.

We demonstrate a seven-core erbium-doped fiber amplifier in which all the cores were pumped simultaneously by a side-coupled tapered multimode fiber. The amplifier has multicore (MC) MC inputs and MC outputs, which can be readily spliced to MC transmission fiber for amplifying space division multiplexed signals. Gain over 25 dB was obtained in each of the cores over a 40-nm bandwidth covering the C-band.

Association study of ARL15 and CDH13 with T2DM in a Han Chinese population.

Several studies indicate that plasma adiponectin levels are associated with the risk of type 2 diabetes mellitus (T2DM) or T2DM risk factors in diverse populations. In addition to the adiponectin gene, several other genes have been postulated to influence plasma adiponectin levels. In this study, we investigated two single nucleotide polymorphisms (SNPs), rs4311394 and rs4783244, located intronically in the ADP-ribosylation factor-like protein 15 (ARL15) and the T-cadherin (CDH13) genes, respectively. These SNPs were detected in a Han Chinese population using a TaqMan assay and evaluated for association with T2DM as well as with individual metabolic traits. Allele frequencies for rs4311394 were significantly different in T2DM and nondiabetes (NDM) groups (χ² = 4.49, P = 0.034). However, neither allele nor genotype frequencies for rs4783244 were associated with T2DM (χ² = 0.33, P = 0.56 and χ² = 2.35, P = 0.31 respectively). The SNPs did not exhibit significant association with individual metabolic traits in the T2DM and NDM groups. Our results indicated that the G allele of the rs4311394 might be a susceptibility factor for T2DM in the Han Chinese population (odds ratio: 1.20; 95% confidence interval: 1.01-1.41).

[Regulatory effect of leonurus extracts on hyperuricemia in rats].

In this study, SD rats were orally administrated with oteracil potassium (300 mg . kg-1 . d-1 ) to prepare the hyperuricemia model, and divided into normal, model, Allopurinol, LE high dosage, middle dosage and low dose (200, 100, 50 mg . kg-1 . d-1) groups. The rats were orally administrated with test drugs 1 hour later after being orally administrated with Oteracil potassium. After 7 days, serum uric acid, serum creatinine, uric acid and expression of relevant transporters in kidney were tested to study the regulatory effect of leonurus extracts on serum uric acid, renal function and relevant transporters in kidney of rats with hyperuricemia. Compared with the model group, the leonurus extract group could significantly down-regulate serum uric acid and creatinine levels of rats with hyperuricemia, and increase the urine uric acid level. Meanwhile, leonurus extracts could notably down-regulate the mRNA expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), up-regulate the mRNA expressions of organic cation transportanter (OCT) and Carnitine transporter (OCTN) and promote the excretion of uric acid of kidney.

Swine Colibacillosis: Analysis of the Gut Bacterial Microbiome.

This study aimed to evaluate the disruption of the swine gut microbiota and histopathological changes caused by infection with enterotoxigenic E. coli. Fecal samples were collected from piglets suffering from diarrhea post-recovery and healthy animals. Intestinal tissues were collected for histopathological changes. The results revealed histopathological changes mainly in the ileum of the infected animals compared to those in the ileum of the control and recovered animals. The operational taxonomic units (OTUs) revealed that the E. coli diarrheal group exhibited the highest bacterial richness. Principal coordinate analysis (PCoA) corroborated the presence of dysbiosis in the gut microbiota following E. coli-induced diarrhea. While the normal control and infected groups displayed slight clustering, the recovery group formed a distinct cluster with a distinct flora. Bacteroidetes, Firmicutes, and Fusobacteria were the dominant phyla in both the healthy and recovered piglets and in the diarrheal group. LEfSe and the associated LDA score analysis revealed that the recovered group exhibited dominance of the phyla Euryarchaeota and Bacteroidota, while groups N and I showed dominance of the phyla Firmicutes and Fusobacteriota, respectively. The LDA scores highlighted a significant expression of the Muribaculacea family in group R. The obtained findings will help in understanding the microbiome during swine colibacillosis, which will support control of the outbreaks.

Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.

Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs.