Zuojinwan (ZJW), a classic herbal formula, has been extensively used to treat gastric symptoms in clinical practice in China for centuries. However, the pharmacological mechanisms of ZJW still remain vague to date. In the present work, a network pharmacology-based strategy was proposed to elucidate its underlying multi-component, multi-target, and multi-pathway mode of action against gastritis. First we collected putative targets of ZJW based on TCMSP and STITCH databases, and a network containing the interactions between the putative targets of ZJW and known therapeutic targets of gastritis was built. Then four topological parameters, “degree”, “betweenness”, “closeness”, and “coreness” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Metacore database to perform a pathway enrichment analysis. A total of 118 nodes including 59 putative targets of ZJW were picked out as major hubs in terms of their topological importance. The results of pathway enrichment analysis indicated that putative targets of ZJW mostly participated in various pathways associated with anti-inflammation response, growth and development promotion and G-protein-coupled receptor signaling. More importantly, five putative targets of ZJW (EGFR, IL-6, IL-1β, TNF-α and MCP-1) and two known therapeutic targets of gastritis (CCKBR and IL-12β) and a link target NF-κB were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZJW acting on gastritis. ZJW could alleviate gastritis through the molecular mechanisms predicted by network pharmacology, and this research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine (TCM) from a holistic perspective.

Breast cancer is the most commonly diagnosed cancer (estimated 2.3 million new cases in 2020) and the leading cause of cancer death (estimated 685,000 deaths in 2020) in women globally. Breast cancers have been categorized into four major molecular subtypes based on the immunohistochemistry (IHC) expression of classic hormone and growth factor receptors including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as a proliferation marker Ki-67 protein expression. Triple-negative breast cancer (TNBC), a breast cancer subtype lacking ER, PR, and HER2 expression, is associated with a high metastatic potential and poor prognosis. TNBC accounts for approximately only 15%–20% of new breast cancer diagnoses; it is responsible for most breast cancer–related deaths due to the lack of targeted treatment options for this patient population, and currently, systemic chemotherapy, radiation, and surgical excision remain the major treatment modalities for these patients with TNBC. Although breast cancer patients in general do not have a robust response to the immunotherapy, a subset of TNBC has been demonstrated to have high tumor mutation burden and high tumor-infiltrating lymphocytes, resembling the features observed on melanoma or lung cancers, which can benefit from the treatment of immune checkpoint inhibitors (ICIs). Therefore, the immunogenic nature of this aggressive disease has presented an opportunity for the development of TNBC-targeting immunotherapies. The recent US Food and Drug Administration approval of atezolizumab in combination with the chemotherapeutic agent nab-paclitaxel for the treatment of PD-L1-positive unresectable, locally advanced, or metastatic TNBC has led to a new era of immunotherapy in TNBC treatment. In addition, immunotherapy becomes an active research area, both in the cancer biology field and in the oncology field. In this review, we will extend our coverage on recent discoveries in preclinical research and early results in clinical trials from immune molecule-based therapy including cytokines, monoclonal antibodies, antibody–drug conjugates, bi-specific or tri-specific antibodies, ICIs, and neoantigen cancer vaccines; oncolytic virus-based therapies and adoptive immune cell transfer–based therapies including TIL, chimeric antigen receptor-T (CAR-T), CAR-NK, CAR-M, and T-cell receptor-T. In the end, we will list a series of the challenges and opportunities in immunotherapy prospectively and reveal novel technologies such as high-throughput single-cell sequencing and CRISPR gene editing-based screening to generate new knowledges of immunotherapy.

Carthamus tinctorius L. is widely used in traditional Chinese medicines for the treatment of cardiovascular disease. However, our current understanding of the molecular mechanisms supporting its clinical application still lags behind. In this study, a systems pharmacology approach integrating drug-likeness evaluation, oral bioavailability prediction, target exploration, GO enrichment analysis, KEGG pathway performance and network construction was adopted to explore its therapeutic mechanism. A total of 21 active ingredients contained in Carthamus tinctorius L. and 113 major proteins were screened out as effective players in the treatment of cardiovascular disease through some related pathways. And the association among the active ingredients, major hubs and main pathways was investigated, implying the potential biological progression of Carthamus tinctorius L. acting on cardiovascular disease. Importantly, the majority of hubs and pathways were found to be highly related with platelet activation process. Core genes that can be regulated by Carthamus tinctorius L. in platelet activation pathway were PRKACA, PIK3R1, MAPK1, PPP1CC, PIK3CA and SYK, and they may play a central role in suppressing platelet aggregation. The systems pharmacology approach used in this study may provide a feasible tool to clarify the mechanism of traditional Chinese medicines and further develop their therapeutic potentials.

Rubus chingii Hu (R. chingii), referred to as "Fu-Pen-Zi" in Chinese, has great medicinal and dietary values since ancient times. The dried fruits of R. chingii have been widely used in traditional Chinese medicine (TCM) for the treatment of kidney enuresis and urinary frequency for centuries. According to current findings, R. chingii has been reported to contain a variety of chemical constituents, mostly triterpenoids, diterpenoids, flavonoids, and organic acids. These compounds have been demonstrated to be the major bioactive components responsible for pharmacological effects such as anticomplementary, anticancer, antioxidant, antimicrobial, and anti-inflammatory functions. Therefore, this review focused on the up-to-date published data of the literature about R. chingii and comprehensively summarized its phytochemistry, pharmacology, quality control, and toxicity to provide a beneficial support to its further investigations and applications in medicines and foods.

Conventional therapy (CT) such as donepezil and memantine are well-known short-term treatments for the symptoms of Alzheimer’s disease (AD). The efficacy of them, however, drops below baseline level after 9 months. In China, herbal therapy as a complementary therapy is very popular. Should conventional therapy combined with herbal therapy (CT + H) make add-on benefit? In this retrospective cohort study, 344 outpatients diagnosed as probable dementia due to AD were collected, with the treatment of either CT + H or CT alone in clinical settings. All the patients were examined with coronary MRI scan. Cognitive functions were obtained by mini–mental state examination (MMSE) every 3 months with the longest follow-up of 24 months. Most of the patients were initially diagnosed with mild (MMSE = 21–26, n = 177) and moderate (MMSE = 10–20, n = 137) dementia. At 18 months, CT+ H patients scored on average 1.76 (P = 0.002) better than CT patients, and at 24 months, patients scored on average 2.52 (P < 0.001) better. At 24 months, the patients with improved cognitive function (△MMSE ≥ 0) in CT + H was more than CT alone (33.33% vs 7.69%, P = 0.020). Interestingly, patients with mild AD received the most robust benefit from CT + H therapy. The deterioration of the cognitive function was largely prevented at 24 months (ΔMMSE = −0.06), a significant improvement from CT alone (ΔMMSE = −2.66, P = 0.005). Compared to CT alone, CT + H significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

Acute respiratory distress syndrome (ARDS) is a complex cascade that develops from acute lung injury (ALI). Ginseng can be used to treat ALI/ARDS. Studies have shown that some of ingredients in ginseng had anti-inflammation, antioxidative, and immune regulation effects and can protect alveolar epithelial cells in mice. However, the potential targets, biological processes, and pathways related to ginseng against ALI/ARDS have not been investigated systematically. We employed network pharmacology, molecular docking, and animal experiments to explore the therapeutic effects and underlying mechanism of action of ginseng against ALI/ARDS. We identified 25 compounds using ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry and their 410 putative targets through database analyses. Sixty-nine of them were considered to be key targets of ginseng against ALI/ARDS according to overlapping with ALI/ARDS-related targets and further screening in a protein–protein interaction (PPI) network. The phosphatidylinositol 3-kinase-protein kinase B (PI3K-AkT) and mitogen-activated protein kinase (MAPK) pathways were recognized to have critical roles for ginseng in ALI/ARDS treatment. Signal transducer and activator of transcription (STAT) 3, vascular endothelial growth factor A (VEGFA), fibroblast growth factor (FGF) 2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), MAPK1, and interleukin (IL) 2 were the top six nodes identified by analyses of a compound–target-pathway network. Molecular docking showed that most of the ingredients in ginseng could combine well with the six nodes. Ginseng could reduce the pathologic damage, neutrophil aggregation, proinflammatory factors, and pulmonary edema in vivo and inhibit the PI3K-Akt signaling pathway and MAPK signaling pathway through downregulating expressions of STAT3, VEGFA, FGF2, PIK3CA, MAPK1, and IL2. Our study provides a theoretical basis for ginseng treatment of ALI/ARDS.