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This state is characterized by severe immunological and metabolic dysfunctions, ultimately leading to multiple organ failure. The underlying pathophysiological mechanisms of sepsis are still unclear, despite extensive basic and clinical studies. Existing therapy still principally consists of basic causative and supportive measures, but adjuvant treatments, such as blood clotting or personalized immunotherapy, are yet to be demonstrated to be very beneficial. This review has discussed the major etiopathogenesis involved in the progression of sepsis and its complications including microcirculation, cytokine storm, oxidative stress, mitochondrial dysfunction, and apoptosis. Further, this article aims to highlight novel biomolecules as effective options available for the treatment of the immunological processes that greatly contribute to sepsis, septic shock and propose a paradigm shift from the pathogen to the host response as a potentially more effective strategy of treating and managing sepsis. We strongly believe that the briefing of these two major fields as recent hallmarks of sepsis research i.e understanding the pathogenesis of sepsis and novel approaches to manage the same in this article, will foster research engagement by clinicians and inventors in this dynamic area and will attract further consideration and sustenance from pharma industry and research laboratories.<\/jats:p>","DOI":"10.1002\/jbt.70522","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:40:58Z","timestamp":1758876058000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["From Molecular Mechanisms of the Pathogenesis of Sepsis to the Novel Healing Biomolecules: Recent Progressions in Dealing With Sepsis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-9432","authenticated-orcid":false,"given":"Deepak","family":"Mishra","sequence":"first","affiliation":[{"name":"Amity Institute of Pharmacy Amity University Uttar Pradesh Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8174-0574","authenticated-orcid":false,"given":"Lucy","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy Amity University Uttar Pradesh Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmanka","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy Amity University Uttar Pradesh Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambit Kumar","family":"Parida","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy Amity University Rajasthan Jaipur Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narhari N.","family":"Palei","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy Amity University Uttar Pradesh Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004875"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060518764717"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.56260\/sciena.v1i4.63"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-021-02735-7"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0000000000000301"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.05.064"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10112412"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0503-3"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370220919076"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/epidemiologia5030032"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00676-y"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105493"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06506-y"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2202707"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.37678\/dcybd.2023.3488"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.11.002"},{"issue":"11","key":"e_1_2_12_18_1","first-page":"80","article-title":"Different Preclinical Animal Models for Sepsis. 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