Rational Design of a Dual-Targeting Natural Toxin-Like Bicyclic Peptide for Selective Bioenergetic Blockage in Cancer Cells.

Stapled α-helical peptides emerge as one of the attractive peptidomimetics which can efficiently penetrate the cell membrane to access intracellular targets. However, the incorporation of a highly lipophilic cross-link may lead to nonspecific membrane toxicity in certain cases. Here, we report a new class of thioether-tethered bicyclic α-helical peptide to mimic the highly constrained loop-helix structure of natural toxins with the dual-targeting ability for both cell-surface receptors and intracellular targets. The thioether cross-links are introduced to replace the redox-sensitive disulfide bonds in natural toxins via a photoinduced thiol-yne reaction followed by macrolactamization. As a proof of concept, αVß3 integrin targeting ligand was grafted into one of the macrocycles in the bicyclic scaffold, while a mitochondria-targeting proapoptotic motif was introduced into the other macrocycle stabilized by an i, i + 7 alkyl thioether cross-link to recapitulate its α-helical conformation. The obtained dual-targeting bicyclic α-helical BIRK peptides showed highly stable α-helical conformation in the presence of denaturants or under high temperature. Notably, BIRK peptides could induce selective cell death in αVß3 integrin-positive B16F10 cells by interfering with the bioenergetic functions of mitochondria. This work provides a new avenue to design and stabilize α-helical peptides in a highly constrained bicyclic loop-helix scaffold with dual functionality.

Application of a social media platform as a patient reminder in the treatment of Helicobacter pylori.

BACKGROUND: To investigate the effect of a social media platform for the treatment of Helicobacter pylori infection. MATERIALS AND METHODS: We enrolled 222 patients from October 2018 to June 2019, who required H pylori therapy. We used WeChat, a social media platform, as a patient reminder tool. They were randomly divided into the intervention and control groups (n = 111 per group) to compare and evaluate their disease awareness, medication adherence, incidence of adverse drug reactions, and H pylori eradication rate. RESULTS: Patients in the intervention group had significantly better disease-related knowledge, medication adherence, and H pylori eradication rates than those in the control group (P < .05). CONCLUSIONS: Using a social media platform may improve treatment rates of H pylori infection.

Giant mucinous liposarcoma of the abdominal cavity: A case report.

RATIONALE: Mucinous liposarcoma myxoid liposarcoma is a malignant mucoid soft tissue tumor derived from undifferentiated stromal cells in perivascular, subbody cavity and intermuscular space, and composed of cells at different stages of differentiation from preadipocytes to mature cells. In rare cases, it may change from lipoma malignancy. The main manifestations is painless mass, relatively slow growth, the course can last decades, the prevalence of liposarcoma in the population is 14% to 18%, mainly in adults, male prevalence is higher than women, but not significant. The main good hair part is the thigh, have mucinous sex, high differentiation type, dedifferentiation type, polymorphic type. Clinical diagnosis is difficult, and there are no obvious symptoms in the early stage, so the diagnosis should be combined with B ultrasound, MRI, CT, and other auxiliary examinations. The gold standard is pathological examination. In December 2023, our department admitted a patient with a mucinous abdominal mass. The report is as follows. PATIENT CONCERNS: Does liposarcoma metastasize? Is any chemotherapy required after surgery? Will it ever relapse in the future? What is the survival period after surgery? DIAGNOSIS: Mucinous liposarcoma. INTERVENTIONS: Surgical resection of the sarcoma. RESULTS: The nodule sample was 33 * 28 * 13 cm, with complete capsule, gray and yellow sections, fine texture, soft, gray, red, grayish, and yellow mucoid nodules in some areas, and the maximum diameter of the nodules was 21cm. Immunohistochemistry was: CD34 (+), CDK 4 (+), CK (-), Desmin (weak +), Ki67 (index 5%), MDM 2 (-), p16 (weak +), S-100P (+), Vimentin (+), BCL-2 (+). He was also sent to the Department of Pathology of Peking Union Medical College Hospital for consultation with Professor Lu Zhaohui, whose consultation opinion was in line with myxoliposarcoma. CONCLUSION: Retroperitoneal liposarcoma is a common retroperitoneal tumor, but it is relatively rare in clinical practice; the overall morbidity is low, mainly manifested as abdominal pain and abdominal distension, abdominal distension, and a long course of disease; it is not sensitive to radiotherapy and chemotherapy, and should be closely follow up by CT examination to understand the recurrence and metastasis.

Hypoxia and ferroptosis.

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis.

Stapling of short cell-penetrating peptides for enhanced tumor cell-and-tissue dual-penetration.

Effective delivery of therapeutics to tumors is generally hampered by the limited penetration of biological barriers imposed by the tumor microenvironment. Despite the broad applications of cell-penetrating peptides (CPPs) for intracellular delivery of therapeutics across membrane bilayers, the discovery of novel CPPs with enhanced tumor tissue permeability remains largely unexplored. Herein, we identified two short stapled CPPs with aromatic cross-links that confer superior dual-penetration in tumor cells and tissues over their linear counterparts. This work may benefit the future applications of constrained CPPs as powerful molecular transporters to access deeper tumor tissues.