Recent studies have found that plant derived microRNA can cross-kingdom regulate the expression of genes in humans and other mammals, thereby resisting diseases. Can exogenous miRNAs cross the blood-prostate barrier and entry prostate then participate in prostate disease treatment? Using HiSeq sequencing and RT-qPCR technology, we detected plant miRNAs that enriched in the prostates of rats among the normal group, BPH model group and rape bee pollen group. To forecast the functions of these miRNAs, the psRobot software and TargetFinder software were used to predict their candidate target genes in rat genome. The qRT-PCR technology was used to validate the expression of candidate target genes. Plant miR5338 was enriched in the posterior lobes of prostate gland of rats fed with rape bee pollen, which was accompanied by the improvement of BPH. Among the predicted target genes of miR5338, Mfn1 was significantly lower in posterior lobes of prostates of rats in the rape bee pollen group than control groups. Further experiments suggested that Mfn1 was highly related to BPH. These results suggesting that plant-derived miR5338 may involve in treatment of rat BPH through inhibiting Mfn1 in prostate. These results will provide more evidence for plant miRNAs cross-kingdom regulation of animal gene, and will provide preliminary theoretical and experimental basis for development of rape bee pollen into innovative health care product or medicine for the treatment of BPH.

Effects of Granule Dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats

The treatment of tumors remains one of the most challenging issues in modern medicine. For a long time, surgical intervention and radiochemotherapy were the primary methods employed to combat tumors; however, the therapeutic outcomes often fell short of expectations. Immunotherapy offers a promising alternative by enhancing the patient’s immune system’s ability to recognize and eliminate tumor cells while minimizing damage to normal cells and tissues. This advancement has brought new hope for cancer patients. In recent years, significant progress has been made in tumor immunotherapy with immune checkpoint inhibitors (ICIs), particularly Programmed Cell Death Protein-1 (PD-1)/Programmed Cell Death-Ligand 1 (PD-L1) inhibitors. An increasing number of researchers have discovered that combination therapy involving PD-1/PD-L1 inhibitors alongside chemotherapeutic agents or other types of ICIs yields more pronounced effects compared to monotherapy. Nevertheless, there remains a considerable risk of developing resistance and experiencing various adverse events. Traditional Chinese medicine (TCM) is frequently utilized as an adjunctive treatment for tumors due to its potential to enhance overall immune function in patients. Recent studies indicate that combining TCM with PD-1/PD-L1 inhibitors can significantly improve median survival times for patients, undoubtedly providing new directions for cancer treatment, however, there remains a lack of sufficient large-sample prospective controlled studies to provide evidence supporting the combined treatment of traditional Chinese medicine and immune checkpoint inhibitors for tumors. This study summarizes recent research on the combined use of PD-1/PD-L1 inhibitors with chemotherapeutic drugs, other ICIs, or TCM in cancer therapy. The aim is to explore their synergistic mechanisms and clinical application value while drawing greater attention from scholars to the significant value of traditional Chinese medicine in the combined treatment strategies for tumors. Additionally, this research provides insights into future prospects for anti-tumor research within TCM.

Yiwei decoction (YWD) is a formula of traditional Chinese medicine (TCM) that is clinically effective for the prevention and treatment of gastric cancer recurrence and metastasis. According to the theory of TCM, YWD tonifies the body and strengthens the body’s resistance to gastric cancer recurrence and metastasis potentially via the immune regulation of the spleen. The aims of the present study were to investigate whether YWD-treated spleen-derived exosomes in rats inhibit the proliferation of tumor cells, to elucidate the anticancer effects of YWD, and to provide evidence supporting the use of YWD as a new clinical treatment for gastric cancer. Spleen-derived exosomes were obtained by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. The location of the exosomes in tumor cells was then determined by immunofluorescence staining. After tumor cells were treated with different concentrations of exosomes, the effect of exosomes on cell proliferation was determined by cell counting kit 8 (CCK8) and colony formation assays. Tumor cell apoptosis was detected by flow cytometry. Particle analysis and western blot analysis identified the material extracted from spleen tissue supernatant as exosomes. Immunofluorescence staining showed that spleen-derived exosomes were taken up by HGC-27 cells, and the CCK8 assay confirmed that the relative tumor inhibition rate of YWD-treated spleen-derived exosomes in the 30 μg/mL reached 70.78% compared to control exosomes in the 30 μg/mL (p < 0.05). Compared to control exosomes in the 30 μg/mL, the colony formation assay indicated that YWD-treated spleen-derived exosomes in the 30 μg/mL colonies have decreased by 99.03% (p < 0.01). Moreover, flow cytometry analysis showed that treatment with YWD-treated exosomes in the 30 μg/mL increased the apoptosis rate to 43.27%, which was significantly higher than that of the control group in the 30 μg/mL (25.91%) (p < 0.05). In conclusion, spleen-derived exosomes from YWD-treated animals inhibit the proliferation of HGC-27 cells via inducing apoptosis, suggesting that spleen-derived exosomes are involved in mediating the antitumor effect of YWD. These results demonstrated a novel exosome-mediated anticancer effect of YWD as a TCM formula, thereby supporting the use of YWD-treated exosomes as a new approach for the clinical treatment of gastric cancer.

Chronic atrophic gastritis (CAG) is an important stage in the transformation of the normal gastric mucosa into gastric cancer. Granule Dendrobii (GD), a proprietary Chinese medicine, has proven clinical efficacy in treating CAG. GD might promote the reversal of precancerous lesions by improving them in CAG patients. However, the mechanism of GD in CAG treatment is relatively less understood. Here, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced CAG rats were treated with GD and its efficacy was evaluated by observing the changes in the rats’ weight and the pathology of gastric tissues. The potential effect of GD on the bacteria was predicted and verified in the large and small intestines and stomachs of CAG rats using amplicon sequencing and RT-qPCR. The results showed that GD could ameliorate the symptoms of body weight loss in CAG rats. Hematoxylin-Eosin (HE) and Alcian Blue (AB) staining showed that GD significantly improved the pathological state of the gastric mucosa in CAG rats. The relative abundance (RA) of Lactobacillus and Turicibacter significantly decreased after GD intervention compared with that of the model group (P < 0.05), indicating that GD might improve CAG by regulating the RA of Lactobacillus and Turicibacter. These findings revealed that Lactobacillus and Turicibacter as bacteria agents associated with gastritis, have the potential to inhibit gastric cancer, especially Turicibacter maybe another pathogen of CAG besides Helicobacter pylori (HP), which is worthy of further study. Meanwhile, the findings provided new ideas and materials for the research and development of new CAG drugs.

Background: Compound dendrobium candidum (CDC) is formulated from Dendrobium candidum and fragrant peony. Preliminary studies have demonstrated that the combination of CDC with conventional antihypertensive medications exhibits significant synergistic effects in lowering blood pressure. The objective of this study was to evaluate the synergistic effect of combining CDC with antihypertensive medications on refractory hypertension in spontaneously hypertensive rats (SHRs) and to elucidate the underlying mechanisms involved. Methods: SHRs were treated with either CDC alone or CDC combined with two or three antihypertensive agents including irbesartan, amlodipine, or terazosin, for a duration of 6 weeks. The alterations in blood pressure, angiotensin II (Ang II), insulin, blood sugar, angiotensin II type I receptor (AT ₁ R), angiotensin II type II receptor (AT ₂ R), insulin receptor, insulin α receptor, and insulin β receptor levels were assessed. Glomerular endothelial cells from refractory SHR were then taken for overexpression and knockdown of AT ₂ R gene and co‐cultured with CDC serum to measure the expression levels of Ang II receptor gene and protein. Results: In comparison to the findings observed in the irbesartan + amlodipine + terazosin (IAT) group, the addition of CDC significantly enhanced antihypertensive efficacy. The rate of achieving blood pressure targets (< 150 mmHg) in SHRs with refractory hypertension increased from 0% to 100%. Treatment with CDC significantly reduced the compensatory increase in AT ₁ R and AT ₂ R levels caused by IAT treatment and showed a significant antihypertensive and synergistic effect. Primary glomerular endothelial cells extracted from SHRs and Wistar rats and treated with 0.5% CDC‐containing serum showed significantly reduced AT ₂ R levels in the AT ₂ R‐overexpression condition. The combination of CDC and antihypertensive drugs was effective in reducing the messenger RNA (mRNA) and protein expression levels of AT ₁ R and AT ₂ R in glomerular endothelial cells. Conclusions: CDC in combination with antihypertensive drugs showed a synergistic effect in controlling refractory hypertension. The mechanism of action may be related to the attenuation of excessive expression of AT ₂ R. This study offers a novel approach for the treatment of clinically resistant hypertension.