Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

OBJECTIVE: Photodynamic therapy has become an important method in clinical tumor treatment. This study aimed to investigate the effects of hematoporphyrin on multiple myeloma (MM) and its potential applications. METHODS: The MM cell line RPMI 8226 was treated with hematoporphyrin derivative (HPD), and CCK-8 assay was used to determine cell viability, apoptosis was detected by flow cytometry, intracellular reactive oxygen species (ROS) levels were measured using a detection kit combined with flow cytometry, and Western blot assay was used to detect apoptosis-related proteins and key signaling pathway protein levels. RESULTS: The optimal incubation time for the maximum absorption of HPD in RPMI 8226 cells was 4 hours. HPD significantly inhibited the proliferation of RPMI 8226 cells in a dose- and illumination time-dependent manner ( r =0.981; r =0.961). Additionally, HPD induced apoptosis in RPMI 8226 cells, but had no significant inhibitory effect on peripheral blood mononuclear cells derived from healthy individuals. HPD combined with illumination treatment significantly increased the intracellular ROS level, upregulated the expression of apoptosis-related proteins such as cleaved PARP, cleaved caspase-3 and Bax, and down-regulated the expression of proteins that maintain cell survival, such as NF-κB and Akt. CONCLUSION The HPD can inhibit the proliferation and induce apoptosis of multiple myeloma cells.
Humans ; Multiple Myeloma/pathology* ; Hematoporphyrins/pharmacology* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Cell Proliferation/drug effects* ; Photochemotherapy ; Cell Survival/drug effects* ; Signal Transduction

Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
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Humans ; Carcinoma, Neuroendocrine/metabolism* ; Signal Transduction ; Animals ; Neoplasm Metastasis ; Neurons/pathology* ; Tumor Microenvironment ; Cell Communication

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.