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.

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.

Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

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 investigate short-term effectiveness of using expert adolescent lateral femoral nail (EALFN) in treating femoral shaft fractures in older children and adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 17 patients with femoral shaft fractures who met the inclusion criteria and were admitted between July 2020 and June 2024. All fractures were fixed with EALFN after reduction. There were 11 males and 6 females, with a mean age of 13.3 years (range, 11-16 years). The average body weight was 51.2 kg (range, 40-84 kg), and the average height was 162.1 cm (range, 150-172 cm). The causes of injury included traffic accidents ( n=9), falling from height ( n=1), and simple falls ( n=7). One patient had an open fracture treated with an external fixator and experienced delayed fracture healing. The remaining patients were closed fractures, with an average time from injury to operation of 5.8 days (range, 2-10 days). Operation time and postoperative hospital stay were documented. During follow-up, X-ray films were taken to observe the fracture healing, and the bilateral femoral length, femoral neck-shaft angle, widest femoral neck diameter (FND), and articular trochanteric distance (ATD) were measured at last follow-up. Hip function was assessed using the Harris score. The differences in the all indicators between the healthy and affected sides were compared. RESULTS: The operation time ranged from 65 to 130 minutes (mean, 94.1 minutes). Postoperative hospital stay ranged from 5 to 40 days (mean, 16.7 days). All patients were followed up 7-36 months (mean, 14.4 months). One patient exhibited delayed fracture healing during follow-up. The distal locking nail was removed at 6 months after operation, and partial weight-bearing was initiated following dynamic fracture stabilization. The fracture healing was achieved, and the intramedullary nail was removed at 24 months after operation. The other fractures healed with the healing time of 6-20 months (mean, 9.6 months), and the intramedullary nails were removed. During follow-up, no femoral fracture, abnormal development of the greater trochanter, or ischemic necrosis of the femoral head occurred. At last follow-up, there was no significant difference in femoral length, femoral neck-shaft angle, FND, ATD, or Harris score between the affected and healthy sides ( P>0.05). CONCLUSION For older children and adolescents with femoral neck fractures, the application of EALFN fixation aligns more closely with the principles of intramedullary central fixation and rapid rehabilitation. This approach is associated with fewer complications and superior short-term effectiveness.
Humans ; Male ; Femoral Fractures/surgery* ; Female ; Child ; Adolescent ; Retrospective Studies ; Bone Nails ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Healing ; Treatment Outcome

OBJECTIVE: To explore the morphological characteristics of the postero-superior protuberance of the calcaneus and to explore its relationship with Haglund malformation. METHODS: Ankle lateral X-ray films of 391 hospitalized patients between May 2021 and June 2024 were retrospectively collected. The morphological parameters of the postero-superior protuberance of the calcaneus were measured, including the length of the base, the height of the base, and the tip angle of the postero-superior protuberance of the calcaneus, and the morphological types were classified according to the above parameters, including the peak type, the hill type, and the flat type. The related parameters of Haglund malformation were measured, including Fowler-Philipp angle (FPA), calcaneal pitch angle (CPA), parallel pitch line (PPL), Chauveaux-Liet angle (CLA), and X/Y ratio (total calcaneal length/length of greater tuberosity of calcaneus). The differences of the morphological parameters of the postero-superior protuberance of the calcaneus and the related indicators of Haglund deformity among the three types and between the males and the females were compared and analyzed, and the differences of the positive numbers of the related indicators of Haglund deformity among the three types were compared. RESULTS: According to the morphological parameters of the postero-superior protuberance of the calcaneus, there were 64 cases of peak type, 245 cases of hill type, and 82 cases of flat type. There was no significant difference in the length of the base of the postero-superior protuberance of the calcaneus, CPA, CLA, and X/Y ratio among the three types ( P>0.05). Among the three types, the peak type had the largest FPA and the flat type had the smallest ( P<0.05); the peak type had the smallest tip angle of the postero-superior protuberance of the calcaneus and the flat type had the largest ( P<0.05); the positive rate of PPL in the hill type was significantly higher than that in the peak type and flat type ( P<0.05); the height of the base of the postero-superior protuberance of the calcaneus in the flat type was the smallest ( P<0.05). FPA, CPA, CLA, PPL, and X/Y ratio were positive in 2, 42, 172, 142, and 77 patients, respectively. There was no significant difference in the number of positive Haglund deformity indicators among the three types ( P>0.05). There was no significant difference between male and female patients in the tip angle of the postero-superior protuberance of the calcaneus, FPA, the positive rate of PPL, and X/Y ratio ( P>0.05). The length and the height of the base of the postero-superior protuberance of the calcaneus, CPA, and CLA in male patients were significantly higher than those in female patients ( P<0.05). CONCLUSION The postero-superior protuberance of the calcaneus can be divided into three types: the peak type, the hill type, and the flat type. The peak type is more likely to suffer from Haglund deformity, and the males are more likely to suffer from Haglund deformity than the females.
Humans ; Calcaneus/anatomy & histology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Radiography ; Child ; Aged

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.
.
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.