PLGA-Astragalus Polysaccharide Nanovaccines Exert Therapeutic Effect in Colorectal Cancer.

Background: Tumor vaccines have achieved remarkable progress in treating patients with various tumors in clinical studies. Nevertheless, extensive research has also revealed that tumor vaccines are not up to expectations for the treatment of solid tumors due to their low immunogenicity. Therefore, there is an urgent need to design a tumor vaccine that can stimulate a broad anti-tumor immune response. Methods: In this work, we developed a nanovaccine (NP-TCL@APS), which includes nanoparticles loaded with colorectal cancer tumor cell lysates (TCL) and Astragalus polysaccharides (APS) into poly (lactic-co-glycolic acid) to induce a robust innate immune response. The NP-TCL@APS was identified by transmission electron microscopy and Malvern laser particle size analyzer. The killing and immune activation effects of NP-TCL@APS were evaluated in vitro. Finally, safety and anti-tumor efficacy were evaluated in the colorectal cancer tumor-bearing mouse model. Results: We found that NP-TCL@APS was preferentially uptaken by DC and further promoted the activation of DC in vitro. Additionally, nanoparticles codelivery of TCL and APS enhanced the antigen-specific CD8+ T cell response and suppressed the growth of tumors in mouse models with good biocompatibility. Conclusion: We successfully prepared a nanovaccine termed NP-TCL@APS, which can promote the maturation of DC and induce strong responses by T lymphocytes to exert anti-tumor effects. The strategy proposed here is promising for generating a tumor vaccine and can be extended to various types of cancers.

Aspirin Inhibits Colorectal Cancer via the TIGIT-BCL2-BAX pathway in T Cells.

The T cell immunoglobulin and ITAM domain (TIGIT) is a recently discovered synergistic co-suppressor molecule that plays an important role in immune response and tumor immune escape in the context of cancer. Importantly, CD155 acts as a receptor for TIGIT, and CD155 signaling to immune cells is mediated through interactions with the co-stimulatory immune receptor CD226 (DNAM-1) and the inhibitory checkpoint receptors TIGIT and CD96. Aspirin (ASA) has been shown to reduce the growth and survival of colorectal cancer (CRC) cells, but the immunological mechanisms involved have not been sufficiently elucidated. In the present study the effects of aspirin on CRC in mice and on Jurkat cells were investigated. Aspirin may suppress the expression of TIGIT on T cells and Regulatory T cells (Tregs) and inhibit T cell viability, and therefore induce tumor cell apoptosis. TIGIT is expressed at higher levels on infiltrating lymphocytes within CRC tumor tissue than adjacent. Further, aspirin could inhibit Jurkat cell proliferation and induce apoptosis via downregulation of TIGIT expression and the anti-apoptosis B cell lymphoma 2 (BCL2) protein and upregulation of BCL2-associated X protein (BAX) expression. The present study suggests that aspirin can inhibit specific aspects of T cell function by reducing interleukin-10 and transforming growth factor-ß1 secretion via the TIGIT-BCL2-BAX signaling pathway, resulting in improved effector T cell function that inhibits tumor progression.

Aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT+Treg cells.

Although aspirin can reduce the incidence of colorectal cancer (CRC), there is still uncertainty about its significance as a treatment for CRC, and the mechanism of aspirin in CRC is not well understood. In this study, we used aspirin to prevent AOM/DSS-induced CRC in mice, and the anti-CRC efficacy of aspirin was assessed using haematoxylin and eosin (H&E) staining and by determining the mouse survival rate and tumour size. 16S rDNA sequencing, flow cytometry (FCM), and Western blotting were also conducted to investigate the changes in the gut microbiota, tumour immune microenvironment, and apoptotic proteins, respectively. The results demonstrated that aspirin significantly exerted anti-CRC effects in mice. According to 16S rDNA sequencing, aspirin regulated the composition of the gut microbiota and dramatically reduced the abundance of Enterococcus cecorum. FCM demonstrated that there were more CD155 tumour cells and CD4 + CD25 + Treg cells showed increased TIGIT levels. Moreover, increased TIGIT expression on Treg cells is associated with reduced Treg cell functionality. Importantly, the inhibition of Treg cells is accompanied by the promotion of CD19 + GL-7 + B cells, CD8 + T cells, CD4 + CCR4 + Th2 cells, and CD4 + CCR6 + Th17 cells. Overall, aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT + Treg cells.

Comprehensive analyses of the ARF gene family in cannabis reveals their potential roles in regulating cannabidiol biosynthesis and male flower development.

Background: Cannabidiol (CBD), as an important therapeutic property of the cannabis plants, is mainly produced in the flower organs. Auxin response factors (ARFs) are play a crucial role in flower development and secondary metabolite production. However, the specific roles of ARF gene family in cannabis remain unknown. Methods: In this study, various bioinformatics analysis of CsARF genes were conducted using online website and bioinformatics, quantitative real time PCR technology was used to investigate the expression patterns of the CsARF gene family in different tissues of different cannabis varieties, and subcellular localization analysis was performed in tobacco leaf. Results: In this study, 22 CsARF genes were identified and found to be unevenly distributed across 9 chromosomes of the cannabis genome. Phylogenetic analysis revealed that the ARF proteins were divided into 4 subgroups. Duplication analysis identified one pair of segmental/whole-genome duplicated CsARF, and three pairs of tandemly duplicated CsARF. Collinearity analysis revealed that two CsARF genes, CsARF4 and CsARF19, were orthologous in both rice and soybean. Furthermore, subcellular localization analysis showed that CsARF2 was localized in the nucleus. Tissue-specific expression analysis revealed that six genes were highly expressed in cannabis male flowers, and among these genes, 3 genes were further found to be highly expressed at different developmental stages of male flowers. Meanwhile, correlation analysis between the expression level of CsARF genes and CBD content in two cultivars 'H8' and 'Y7' showed that the expression level of CsARF13 was negatively correlated with CBD content, while the expression levels of six genes were positively correlated with CBD content. In addition, most of CsARF genes were responsive to IAA treatment. Conclusion: Our study laid a foundation for the further studies of CsARFs function in cannabis, and provides candidate genes for breeding varieties with high CBD yield in cannabis production.

Discovery of potent and novel dual NAMPT/BRD4 inhibitors for efficient treatment of hepatocellular carcinoma.

The NAPRT-induced increase in NAD+ levels was proposed as a mechanism contributing to hepatocellular carcinoma (HCC) resistance to NAMPT inhibitors. Thus, concurrently targeting NAMPT and NAPRT could be considered to overcome drug resistance. A BRD4 inhibitor downregulates the expression of NAPRT in HCC, and the combination of NAMPT inhibitors with BRD4 inhibitors simultaneously blocks NAD+ generation via salvage and the PH synthesis pathway. Moreover, the combination of the two agents significantly downregulated the expression of tumor-promoting genes and strongly promoted apoptosis. The present work identified various NAMPT/BRD4 dual inhibitors based on the multitargeted drug rationale. Among them, compound A2, which demonstrated the strongest effect, exhibited potent inhibition of NAMPT and BRD4 (IC50 = 35 and 58 nM, respectively). It significantly suppressed the growth and migration of HCC cells and facilitated their apoptosis. Furthermore, compound A2 also manifested a robust anticancer effect in HCCLM3 xenograft mouse models, with no apparent toxic effects. Our findings in this study provide an effective approach to target NAD+ metabolism for HCC treatment.

tiRNA-Val-CAC-2 interacts with FUBP1 to promote pancreatic cancer metastasis by activating c­MYC transcription.

Cumulative studies have established the significance of transfer RNA-derived small RNA (tsRNA) in tumorigenesis and progression. Nevertheless, its function and mechanism in pancreatic cancer metastasis remain largely unclear. Here, we screened and identified tiRNA-Val-CAC-2 as highly expressed in pancreatic cancer metastasis samples by tsRNA sequencing. We also observed elevated levels of tiRNA-Val-CAC-2 in the serum of pancreatic cancer patients who developed metastasis, and patients with high levels of tiRNA-Val-CAC-2 exhibited a worse prognosis. Additionally, knockdown of tiRNA-Val-CAC-2 inhibited the metastasis of pancreatic cancer in vivo and in vitro, while overexpression of tiRNA-Val-CAC-2 promoted the metastasis of pancreatic cancer. Mechanically, we discovered that tiRNA-Val-CAC-2 interacts with FUBP1, leading to enhanced stability of FUBP1 protein and increased FUBP1 enrichment in the c-MYC promoter region, thereby boosting the transcription of c-MYC. Of note, rescue experiments confirmed that tiRNA-Val-CAC-2 could influence pancreatic cancer metastasis via FUBP1-mediated c-MYC transcription. These findings highlight a potential novel mechanism underlying pancreatic cancer metastasis, and suggest that both tiRNA-Val-CAC-2 and FUBP1 could serve as promising prognostic biomarkers and potential therapeutic targets for pancreatic cancer.

Triplane technique for breast reconstruction after breast cancer surgery: A case series report.

RATIONALE: Implant-based breast reconstruction is an important method for post-mastectomy breast reconstruction. Currently, the most commonly used technique is the biplane technique. However, the high rate of postoperative complications, the inability of pockets to accommodate larger implants, and the expensive costs of biological mesh make the development of new surgical methods urgent. The triplane technique for breast reconstruction is an ideal candidate method. PATIENT CONCERNS: The main local symptoms were breast lump, abnormal breast skin, nipple discharge, and abnormal nipple or areola in 24 patients. DIAGNOSES: The study included 24 female patients who underwent breast reconstruction using the triplane technique after radical breast cancer surgery. INTERVENTIONS: The surgical procedure involved measuring the dimensions of the breast, designing the incision, and creating a pocket for the implant using the triplane technique, which includes the pectoralis major muscle, the pectoralis major fascia continuing to the rectus abdominis fascia, and the latissimus dorsa muscle fascia continuing to the rectus abdominis fascia. Postoperative follow-up included regular assessments of pain and evaluation of breast appearance. OUTCOMES: No cases of postoperative infection were observed in all patients. During the 1-year follow-up period after surgery, 5 patients (20.8%) who needed radiotherapy after mastectomy for cancer showed slight darkening of skin flap pigment after using the triplane technique implant. No cases of exposure or infection of the expanders were reported, and 1 patient underwent expander replacement with a permanent prosthesis. All patients expressed satisfaction with the reconstructed breast shape. The 10 patients (41.7%) experiencing postoperative swelling and pain. However, the pain gradually subsided during the postoperative recovery period. No cases of local recurrence or distant metastasis of breast cancer were observed during the 1-year-follow-up period. LESSONS: The triplane technique for breast reconstruction after breast cancer surgery provides good implant coverage, reduces the risk of complications, and is cost-effective.

Integrated network pharmacology and experimental verification to explore the potential mechanism of San Ying decoction for treating triple-negative breast cancer.

Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.

Research progress of LSD1-based dual-target agents for cancer therapy.

Lysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1 inhibitors synergistically improve the efficacy of additional antitumor drugs, which encourages numerous medicinal chemists to innovate and develop new-generation LSD1-based dual-target agents. This review discusses the theoretical foundation of the design of LSD1-based dual-target agents and summarizes their possible applications in treating cancers.

Xianlinglianxiafang Inhibited the growth and metastasis of triple-negative breast cancer via activating PPARγ/AMPK signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasion and metastasis rates. Xian-Ling-Lian-Xia formula (XLLX) is a traditional Chinese medicine prescription widely used in China for treating TNBC. Clinical studies have shown that XLLX significantly reduces the recurrence and metastasis rate of TNBC and improves disease-free survival. However, the potential molecular mechanisms of XLLX on TNBC are not clear yet. Here, we investigated the effects of XLLX on TNBC using a mouse model and tumor cell lines. The results showed that XLLX significantly inhibited the proliferation, migration, and invasion abilities of TNBC cell lines MDA-MB-231 and 4T1 in vitro, induced apoptosis, and regulated the expression of proliferation, apoptosis, and EMT marker proteins in tumor cells. In in vivo experiments, XLLX treatment significantly reduced the progression of TNBC tumors and lung metastasis. Transcriptomics reveals that XLLX treatment significantly enriched differentially expressed genes in the peroxisome proliferator-activated receptor gamma (PPARγ) and AMP-dependent protein kinase (AMPK) signaling pathways. The western blot results confirmed that XLLX significantly upregulated the protein expression of PPARγ and p-AMPK in TNBC cells, tumors, and lung tissues. It is noteworthy that GW9662 (a PPARγ inhibitor) and Compound C (an AMPK inhibitor) partially reversed the anti-proliferation and anti-metastasis effects of XLLX in TNBC cells. Therefore, XLLX may effectively inhibit the growth and metastasis of TNBC by activating the PPARγ/AMPK signaling pathway.

Research progress of STAT3-based dual inhibitors for cancer therapy.

Signal transducer and activator of transcription 3 (STAT3), a transcription factor, regulates gene levels that are associated with cell survival, cell cycle, and immune reaction. It is correlated with the grade of malignancy and the development of various cancers and targeting STAT3 protein is a potentially promising therapeutic strategy for tumors. Over the past 20 years, various compounds have been found to directly inhibit STAT3 activity via different strategies. However, numerous difficulties exist in the development of STAT3 inhibitors, such as serious toxic effects, poor therapeutic effects, and intrinsic and acquired drug resistance. STAT3 inhibitors synergistically suppress cancer development with additional anti-tumor drugs, such as indoleamine 2,3-dioxygenase 1 inhibitors (IDO1i), histone deacetylase inhibitors (HDACi), DNA inhibitors, pro-tumorigenic cytokine inhibitors (PTCi), NF-κB inhibitors, and tubulin inhibitors. Therefore, individual molecule- based dual-target inhibitors can be the candidate alternative or complementary treatment to overcome the disadvantages of just STAT3 or other targets as a monotherapy. In this review, we discuss the theoretical basis for formulating STAT3-based dual-target inhibitors and also summarize their structure-activity relationships (SARs).

The dual role of p63 in cancer.

The p53 family is made up of three transcription factors: p53, p63, and p73. These proteins are well-known regulators of cell function and play a crucial role in controlling various processes related to cancer progression, including cell division, proliferation, genomic stability, cell cycle arrest, senescence, and apoptosis. In response to extra- or intracellular stress or oncogenic stimulation, all members of the p53 family are mutated in structure or altered in expression levels to affect the signaling network, coordinating many other pivotal cellular processes. P63 exists as two main isoforms (TAp63 and ΔNp63) that have been contrastingly discovered; the TA and ΔN isoforms exhibit distinguished properties by promoting or inhibiting cancer progression. As such, p63 isoforms comprise a fully mysterious and challenging regulatory pathway. Recent studies have revealed the intricate role of p63 in regulating the DNA damage response (DDR) and its impact on diverse cellular processes. In this review, we will highlight the significance of how p63 isoforms respond to DNA damage and cancer stem cells, as well as the dual role of TAp63 and ΔNp63 in cancer.

Recent advances in EZH2-based dual inhibitors in the treatment of cancers.

The enhancer of zeste homolog 2 (EZH2) protein is the catalytic subunit of one of the histone methyltransferases. EZH2 catalyzes the trimethylation of lysine 27 of histone H3 (H3K27me3) and further alters downstream target levels. EZH2 is upregulated in cancer tissues, wherein its levels correlate strongly with cancer genesis, progression, metastasis, and invasion. Consequently, it has emerged as a novel anticancer therapeutic target. Nonetheless, developing EZH2 inhibitors (EZH2i) has encountered numerous difficulties, such as pre-clinical drug resistance and poor therapeutic effect. The EZH2i synergistically suppresses cancers when used in combination with additional antitumor drugs, such as PARP inhibitors, HDAC inhibitors, BRD4 inhibitors, EZH1 inhibitors, and EHMT2 inhibitors. Typically, the use of dual inhibitors of two different targets mediated by one individual molecule has been recognized as the preferred approach for overcoming the limitations of EZH2 monotherapy. The present review discusses the theoretical basis for designing EZH2-based dual-target inhibitors, and also describes some in vitro and in vivo analysis results.

Design, synthesis, and biological evaluation of novel napabucasin-melatonin hybrids as potent STAT3 inhibitors.

The current work developed diverse novel napabucasin-melatonin hybrids as potent STAT3 inhibitors. Several biological studies have suggested many compounds demonstrating potent inhibition against different tumor cells. Among these, compound 7e depicted enhanced inhibition against HepG2, MDA-MB-231, and A549 cells than napabucasin, with IC50 values of 1.06, 1.38, and 1.3 µM, respectively. Based on fluorescence polarization analysis, compound 7e was bound to the SH2 domain in STAT3, with an IC50 value of 12.95 µM. Molecular docking further confirmed the 7e binding mode inside the SH2 domain of STAT3. Further mechanistic studies indicated that 7e inhibited the activation of STAT3 (Y705), and thus reduced the expression of STAT3 downstream genes (CyclinD1, Bcl-2 and c-Myc) instead of affecting p-STAT1 expression. Meanwhile, the phosphorylation levels of its upstream kinases JAK2 and bypass kinase Erk1/2 remain unaffected. Simultaneously, 7e induced cancer cell apoptosis in a concentration-dependent manner. Significantly, 20 mg/kg (i.p.) compound 7e suppressed the mouse HepG2 xenograft development in vivo without body weight loss, suggesting that it could be an effective antitumor agent.

Dapagliflozin delays renal fibrosis in diabetic kidney disease by inhibiting YAP/TAZ activation.

In diabetic kidney disease (DKD), the long-term hyperactivation of yes-associated protein (YAP)/transcriptional coactivator PDZ-binding motif (TAZ) in renal proximal tubule epithelial cells (RPTCs) plays an important role in progressive tubulointerstitial fibrosis. Sodium-glucose cotransporter 2 (SGLT2) is highly expressed in RPTCs, but its relationship with YAP/TAZ in tubulointerstitial fibrosis in DKD is still unknown. The purpose of this study was to clarify whether the SGLT2 inhibitor (SGLT2i) dapagliflozin could alleviate renal tubulointerstitial fibrosis in DKD by regulating YAP/TAZ. We examined 58 patients with DKD confirmed by renal biopsy and found that the expression and nuclear translocation of YAP/TAZ increased with the exacerbation of chronic kidney disease classification. In models of DKD, dapagliflozin showed similar effects to verteporfin, an inhibitor of YAP/TAZ, in reducing the activation of YAP/TAZ and downregulating the expression of their target genes, connective tissue growth factor (CTGF) and amphiregulin in vivo and in vitro. Silencing SGLT2 also confirmed this effect. Importantly, dapagliflozin showed a better effect than verteporfin in inhibiting inflammation, oxidative stress and fibrosis in the kidney in DKD rats. Taken together, this study proved for the first time that dapagliflozin delayed tubulointerstitial fibrosis at least partly by inhibiting YAP/TAZ activation, which further enriched the antifibrotic effect of SGLT2i.

Daucosterol combined with umbilical cord mesenchymal stem cell-derived exosomes can alleviate liver damage in liver failure mice by regulating the IL-6/STAT3 signaling pathway.

Daucosterol is a phytosterol glycoside with hepatoprotective properties. The objective of the present study was to confirm the role of daucosterol in liver failure. Exosomes were isolated from primary mouse umbilical cord mesenchymal stem cells (UCMSCs). A liver failure mouse model was generated by injecting lipopolysaccharide/D-galactosamine. Mice were treated with exosomes alone or in combination with daucosterol (5, 10, or 20 mg/kg). Liver tissue damage was examined by hematoxylin-eosin, Masson's trichrome, and TUNEL staining. The levels of genes, proteins, and inflammatory factors were determined using real-time qPCR, western blotting, and enzyme-linked immunosorbent assay, respectively. Compared with normal mice, we noted severe damage, fibrosis, and apoptosis in the liver tissues of liver failure-induced mice. UCMSC-derived exosomes effectively alleviated hepatic damage in the mouse model. Compared with exosome treatment alone, exosomes combined with daucosterol significantly and dose-dependently reduced pathological changes in model mice. Exosome treatment alone or combined with daucosterol also markedly decreased the liver index and reduced levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in model mice. Exosome treatment alone or combined with daucosterol suppressed mRNA expression levels of IL-6 and signal transducer and activator of transcription (STAT3) and STAT3 protein expression in model mice. Our findings revealed that treatment with daucosterol combined with UCMSC-derived exosomes was superior to exosomes alone for alleviating hepatic damage in mice with liver failure by regulating the IL-6/STAT3 signaling pathway. Accordingly, daucosterol combined with UCMSC-derived exosomes may be a prospective treatment strategy for liver failure.

Probiotic powder ameliorates colorectal cancer by regulating Bifidobacterium animalis, Clostridium cocleatum, and immune cell composition.

Based on the relationship between the gut microbiota and colorectal cancer, we developed a new probiotic powder for treatment of colorectal cancer. Initially, we evaluated the effect of the probiotic powder on CRC using hematoxylin and eosin staining, and evaluated mouse survival rate and tumor size. We then investigated the effects of the probiotic powder on the gut microbiota, immune cells, and apoptotic proteins using 16S rDNA sequencing, flow cytometry, and western blot, respectively. The results showed that the probiotic powder improved the intestinal barrier integrity, survival rate, and reduced tumor size in CRC mice. This effect was associated with changes in the gut microbiota. Specifically, the probiotic powder increased the abundance of Bifidobacterium animalis and reduced the abundance of Clostridium cocleatum. In addition, the probiotic powder resulted in decreased numbers of CD4+ Foxp3+ Treg cells, increased numbers of IFN-γ+ CD8+ T cells and CD4+ IL-4+ Th2 cells, decreased expression of the TIGIT in CD4+ IL-4+ Th2 cells, and increased numbers of CD19+ GL-7+ B cells. Furthermore, the expression of the pro-apoptotic protein BAX was significantly increased in tumor tissues in response to the probiotic powder. In summary, the probiotic powder ameliorated CRC by regulating the gut microbiota, reducing Treg cell abundance, promoting the number of IFN-γ+ CD8+ T cells, increasing Th2 cell abundance, inhibiting the expression of TIGIT in Th2 cells, and increasing B cell abundance in the immune microenvironment of CRC, thereby increasing the expression of BAX in CRC.

Severe persistent mycobacteria antigen stimulation causes lymphopenia through impairing hematopoiesis.

Miliary tubersculosis (TB), an acute systemic blood disseminated tuberculosis mainly caused by Mycobacterium tuberculosis (M. tuberculosis), can cause signs of lymphopenia in clinical patients. To investigate whether/how persistent mycobacteria antigen stimulation impairs hematopoiesis and the therapeutic effect of interleukin-7 (IL-7), a mouse model of Mycobacterium Bovis Bacillus Calmette-Guérin (BCG) intravenous infection with/without an additional stimulation with M. tuberculosis multi-antigen cocktail containing ESAT6-CFP10 (EC) and Mtb10.4-HspX (MH) was established. Consistent with what happened in miliary TB, high dose of BCG intravenous infection with/without additional antigen stimulation caused lymphopenia in peripheral blood. In which, the levels of cytokines IFN-γ and TNF-α in serum increased, and consequently the expression levels of transcription factors Batf2 and IRF8 involved in myeloid differentiation were up-regulated, while the expression levels of transcription factors GATA2 and NOTCH1 involved in lymphoid commitment were down-regulated, and the proliferating activity of bone marrow (BM) lineage- c-Kit+ (LK) cells decreased. Furthermore, recombinant Adeno-Associated Virus 2-mediated IL-7 (rAAV2-IL-7) treatment could significantly promote the elevation of BM lymphoid progenitors. It suggests that persistent mycobacteria antigen stimulation impaired lymphopoiesis of BM hematopoiesis, which could be restored by complement of IL-7.