Annals of medicine
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Sepsis is still the leading cause of death as a result of infection. Metabolic disorder plays a vital role in sepsis progression. Glycolysis intensification is the most characteristic feature of sepsis-related metabolic disorders. ⋯ KEY MESSAGESepsis induces high expression of PFKFB3 in immunocytes and nonimmune cells, thereby enhancing cellular glycolytic flux. PFKFB3-driven glycolysis reprogramming is closely related to an excessive inflammatory response and high mortality in sepsis. Inhibition of PFKFB3 alone or in combination provides a novel combinatorial therapeutic target for sepsis.
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Altered epigenetic map is frequently observed in cancer and recent investigations have demonstrated a pertinent role of epigenetic modifications in the response to many anticancer drugs including the DNA damaging agents. Topoisomerase I (Top I) is a well-known nuclear enzyme that is critical for DNA function and cell survival and its inhibition causes DNA strand breaks and cell cycle arrest. Inhibitors of human Top I have proven to be a prosperous chemotherapeutic treatment for a vast number of cancer patients. While the treatment is efficacious in many cases, resistance and altered cellular response remain major therapeutic issues. ⋯ The field of epigenetic research is steadily growing. With its assistance, we could gain better understanding on how drug response and resistance work. Epigenetics can evolve as possible biomarkers and predictors of response to many medications including Top I inhibitors, and could have significant clinical implications that necessitate deeper attention.HIGHLIGHTSEpigenetic alterations, including DNA methylation and histone modifications, play a pertinent role in the response to several anticancer treatments, including DNA damaging agents like Top I inhibitors.Although camptothecin derivatives are used clinically as Top I inhibitors for management of cancer, certain types of cancer have inherent and or acquired resistance that limit the curative potential of them.Epigenetic modifications like DNA hypomethylation can either increase or decrease sensitivity to Top I inhibitors by different mechanisms.The combination of Top I inhibitors with the inhibitors of histone modifying enzymes can result in enhanced cytotoxic effects and sensitization of resistant cells to Top I inhibitors.MicroRNAs were found to directly influence the expression of Top I and other proteins in cancer cells resulting in positive or negative alteration of the response to Top I inhibitors.lncRNAs and their genetic polymorphisms have been found to be associated with Top I function and the response to its inhibitors.Clinical trials of epigenetic drugs in combination with Top I inhibitors are plentiful and some of them showed potentially promising outcomes.
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Breast abscess is a common and intractable clinical condition and the use of needle aspiration (NA) or incision and drainage (ID) in treatment is controversial. This meta-analysis aimed to systematically compare the clinical effectiveness of NA and ID in treating breast abscesses. ⋯ NA has better advantages in terms of healing time, avoidance of breast fistula, continuous breastfeeding, and patient satisfaction. Although NA and ID have similar cure and recurrence rates, NA, with or without ultrasound guidance, could be used as a first-line treatment for breast abscesses. Patients with large volumes, multicompartmental abscesses, or those who have been ineffective against multiple NA, should be considered for ID.KEY MESSAGESBreast abscess is a common and intractable clinical condition in general surgery.Compared with ID for breast abscesses, NA has better advantages in terms of healing time, avoidance of breast fistula, continuous breastfeeding, and patient satisfaction and could be used as a first-line treatment for breast abscesses.Patients with large volumes, multicompartmental abscesses, or those who have been ineffective against multiple NA, should be considered for ID.
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Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard therapies. ⋯ VEN-containing regimens could be suggested as effective and safe treatments to RR MM patients with t(11;14) or high BCL-2 levels.
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The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. ⋯ Key MessagesCCL5 plays dual roles in colorectal cancer progression. CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action. CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.