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Immune monitoring, immune phenotyping, and precision intervention in severe pneumonia: current evidence and translational challenges

Severe pneumonia remains a major cause of mortality in critically ill patients, with severe community-acquired pneumonia representing a clinically important and representative scenario. This review focuses primarily on severe community-acquired pneumonia as the clinical context, in which outcomes are determined by the interplay between pathogen burden and heterogeneity of host responses. Beyond pathogen-directed therapies, severe pneumonia is frequently characterized by dynamic and partially overlapping states of hyperinflammation, immune dysfunction, and subsequent immunosuppression. Differen

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… In contrast, thymosin alpha 1 has demonstrated potential immunomodulatory effects and signals of clinical benefit in studies of COVID-19 and sepsis; however, the available evidence remains inconsistent. … Moreover, a recent randomized controlled trial in adults with sepsis failed to demonstrate a significant reduction in 28-day mortality with thymosin alpha 1 treatment ( 113 ). …

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation.

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specific

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… Recently, Aslam and coauthors [ 100 ] reported the production and respective purification of IFNα-2-thymosin α1 fusion protein (IFNα-2 in combination with thymosin α1) in E. coli. IFNα-2-thymosin α1 fusion protein was expressed with 6xHis-tag at C -terminus. … In sum, due to the observed synergistic effect, IFNα-2-thymosin α1 fusion protein showed significantly higher anticancer activity in comparison with the individual contribution of both polypeptidic chains [ 100 ]. …

Abscopal Effect in Radiation Therapy: The Immune Mechanisms and Clinical Advances.

The abscopal effect is a systemic antitumor response to localized radiotherapy (RT) that has emerged as a central focus in the era of immunotherapy. Clinical evidence demonstrates that local RT can induce regression of distant, nonirradiated metastases, including cases of complete remission. However, the effect remains unpredictable, with marked variation in clinical outcomes ranging from complete regression to paradoxical progression. The mechanistic basis for this heterogeneity and optimal strategies to enhance abscopal effects remain incompletely understood. This review synthesizes current

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… NCT02976740 | GM‐CSF + T cell activation (thymosin α1) + RT | II | Unknown | NSCLC (Stage IV, failed second‐line chemotherapy) | SBRT + rhGM‐CSF + thymosin alpha‐1 | Combination approach. Primary: Abscopal effect rate at 4 weeks after combined treatment completion. … Thymalfasin (thymosin α1) NCT02535988 | Thymalfasin + RT | II | Withdrawn | Colorectal cancer (Stage IV) | RT + thymalfasin | Withdrawn. Planned endpoint: Proportion of patients with abscopal response at 7–8 weeks. …

Pharmacological interventions for acute pancreatitis.

BACKGROUND: In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care … cs, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this …

[Clinical analysis of the first patient with imported Middle East respiratory syndrome in China].

OBJECTIVE: To report the treatment of the first imported Middle East respiratory syndrome ( MERS ) in China, and to investigate the clinical … meropenem 2.0 g, q8h on the 7th day for 2 weeks. Gamma globulin was given for 7 days ( 20 g, qd ). Thymosin-α1 was given on the 8th day for 2 weeks. Interferon was given once a week, but only one dose was used. At the same time symptomatic treatment such as methimazole and liver protection therapy were given. (4) Patient began to cough at admission, and i …

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administr

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… NCT04304313 | 10 | - Siltuximab | NCT04329650 | 100 | compared to methylprednisolone Sirolimus | NCT04341675 | 30 | - Sofosbuvir/Daclatasvir | IRCT20200128 046294N2 | 70 | compared to standard treatment Tacrolimus | NCT04341038 | 84 | compared to standard treatment; combined with methylprednisolone Thymosin … | ChiCTR20000 29541 | 100 | combined with darunavir/cobicistat or lopinavir/ritonavir Thymosin | ChiCTR20000 29806 | 120 | compared to Camrelizumab and conventional treatment TJ003234 | NCT04341116 | 144 | - Tocilizumab | ChiCTR20000 29765 | 188 | compared to standard treatment Tocilizumab | ChiCTR20000 …

Radix Sophorae flavescentis versus other drugs or herbs for chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) infection is a liver disease caused by hepatitis B virus, which may lead to serious complications such a … o 12 months. The drugs being used as a comparator were lamivudine, adefovir, interferon, tiopronin, thymosin, or other Chinese herbs. Two trials included children up to 14 years old. Participants in one trial had cirrhosis in chronic hepatitis B. None of the trials reported all-cause mortality, health-related quality of life, serious adverse events, hepati …

[Risk factors of death in patients with bloodstream infections in a medical intensive care unit].

OBJECTIVE: To analyze the incidence, etiological characteristics, and risk factors for death in patients with bloodstream infection in a med … lcitonin (PCT), etc.], clinical management (red blood cell transfusion and usage of immunoglobulin, thymosin α1, glucocorticoid, empirical antibiotic therapy, mechanical ventilation, renal replacement therapy, etc.), and prognostic indicators (length of medical ICU stay and length of hospital stay after bloodstream infection). All patients were followed up …

The Mechanism and Clinical Outcome of patients with Corona Virus Disease 2019 Whose Nucleic Acid Test has changed from negative to positive, and the therapeutic efficacy of Favipiravir: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: A variety of possible mechanisms can make the nucleic acid test of patients who meet the discharge conditions positive again, in … administered, this includes oxygen therapy, drugs that reduced phlegm and relieve cough, including thymosin, proprietary Chinese medicine, etc. MAIN OUTCOMES: Primary Outcome Measures: Viral nucleic acid test negative [Time Frame: 5 months]: Subjects who tested negative for nucleic acid from sputum or nasopharyngeal swabs for two consecutive times (sampli …

Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy and mode of action.

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be

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… Thymophysin and α -1-Thymosin Among the experimental strategies targeting HCC, immunomodulation is considered to be a promising strategy. … Likewise, immune function depression was found to play a major role in the development and pathogenesis of HCC. 106 Thymostimulin, a thymic peptide fraction isolated from calf thymus including thymosin-α-1 and thymic humoral factor, was found to be an effective immunomodulatory agent. 107 It is capable …

Successful salvage of a severe COVID-19 patient previously with lung cancer and radiation pneumonitis by mesenchymal stem cells: a case report and literature review.

During the COVID-19 pandemic, elderly patients with underlying condition, such as tumors, had poor prognoses after progressing to severe pneumonia and often had poor response to standard treatment. Mesenchymal stem cells (MSCs) may be a promising treatment for patients with severe pneumonia, but MSCs are rarely used for patients with carcinoma. Here, we reported a 67-year-old female patient with lung adenocarcinoma who underwent osimertinib and radiotherapy and suffered from radiation pneumonitis. Unfortunately, she contracted COVID-19 and that rapidly progressed to severe pneumonia. She respo

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… Treatment before MSCs | MSCs type | MSCs administration (cells/time) | Efficacy (from initial MSCs) | Notes Liang 2020 ( 82 ) | China | F | 65 | Hypertension, Diabetes | MOF, Gastrorrhagia Hemolysis | IFN-α inhalation, Lopinavir/Ritonavir, Moxifloxacin, Xuebijing, Methylprednisolone, Immunoglobulin, Thymosin … Zhang 2020 ( 86 ) | China | M | 54 | Diabetes | No | Lopinavir/Ritonavir, IFN-Α Inhalation, Levofloxacin, Tanreqing capsule, Xuebijing, Thymosin α1, Methylprednisolone, Immunoglobulin Plasma Exchange. | UC | 1×10 6 /kg VD | Remission | Discharged from ICU on day 2 Eckard 2020 ( 87 ) | America | M | 4 …

Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy.

Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls of conventional anticancer therapies such as systematic toxicity, compromised life quality, and limited to severe side effects are major areas of concern of conventional cancer treatment approaches. Owing to the expansion of knowledge and technological advancements in the field of cancer biology, more innovative and safe anti-cancerous approaches such as immune therapy, gene therapy and targeted therapy a

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… Our recent findings highlight the atypical involvement of PI3K-Akt kinases and p53 in triggering both cell death and resistance, facilitated by the FDA-approved thymosin beta 4 (Tβ4) drug in medulloblastoma (MB) cells [ 77 , 78 ]. … Naeem A, Knoer G, Laura Avantaggiati M, Rodriguez O, Albanese C (2023) Provocative non-canonical roles of p53 and AKT signaling: a role for thymosin β4 in medulloblastoma. Int Immunopharmacol 116:109785. 10.1016/j.intimp.2023.109785 80. …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

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… It was proven both in vitro and in vivo that the addition of thymosin α1 following oncolytic Ad administration induces the generation of an anti‐tumoural phenotype of macrophages, increasing anti‐tumoural immunity. … Thymosin α1 reverses oncolytic adenovirus‐induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy. Cell Rep Med. 2024;5(10):101751. 10.1016/j.xcrm.2024.101751 51. Wennier ST, Liu J, McFadden G. …

Гетерогенность регулируемых клеток В в аутоиммунных заболеваниях: последствия для иммунного равновесия и терапевтических стратегий.

Регулирующие клетки В (Bregs) играют ключевую роль в поддержании иммунной терпимости и профилактике аутоиммунных заболеваний. Однако в условиях аутоиммунной среды количество и функции брега часто ухудшаются, что ведет к провоспалительной микроокружающей среде и регулированию иммунной дизакции. В рамках этого обзора проводится углубленный анализ последствий различных аутоиммунных заболеваний, включая множественный склероз, ревматоидный артрит, системный волчанье эритематосус, болезнь Шёгрена, аутоиммунный диабет и другие аутоиммунные заболевания. Резюмируя изменения в фенотипе Брегса и его функ

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… function of both human and murine B10 cells, reducing Th17 and Tfh. [ 97 ] CpG: restoring IL-10 expression [ 100 ] Improving Bregs expansion Thioredoxin stimulation: restoring Bregs from patients with SLE to healthy levels [ 13 ] Blocking SLAMF5 (CD84): mitigating EAE and increasing Breg levels [ 28 ] Thymosin-α1 …

Repurposing Anti-Cancer Drugs for COVID-19 Treatment.

The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards identifying effective drugs and developing novel vaccines. Early data from Adaptive COVID-19 Treatment Trials

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… Tofacitinib NCT04390061 Not yet recruiting Hydroxychloroquine Phase 2 54 Tofacitinib NCT04412252 Not yet recruiting None Phase 2 240 Interferon IFN-A1B NCT04293887 Not yet recruiting None Phase 1 328 IFN-A2B NCT04349410 Enrolling by invitation None Phase 2/3 500 Nasal IFN-A1B NCT04320238 Recruiting Anti-thymosin … Hydroxychloroquine | Phase 2 | 54 Tofacitinib | NCT04412252 | Not yet recruiting | None | Phase 2 | 240 Interferon | IFN-A1B | NCT04293887 | Not yet recruiting | None | Phase 1 | 328 IFN-A2B | NCT04349410 | Enrolling by invitation | None | Phase 2/3 | 500 Nasal IFN-A1B | NCT04320238 | Recruiting | Anti-thymosin …

Keyword Index for Volume 107

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… regulation 1844 telomere 1844 telomere length 1525 temozolomide 1399 TERT–CLPTM1L 1001 testicular cancer 1833 testicular germ cell tumour 1754, 1853 TFT 429 TGF- β -activated kinase-1 129 the Glasgow Prognostic Score 988 The Netherlands 12 therapeutic target 63 third primary cancer 549 thymosin …

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

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… Kynurenine 3-monooxygenase; Kyn Kynurenine; KYNU 2-amino-4-[3-hydroxyphenyl]-4-hydroxybutanoic acid; Leu Leucine; LPS Lipopolysaccharide; SLC Solute carrier; STAT3 Signal transducer and activator of transcription 3; TAM Tumor-associated macrophages; TGF Transforming growth factor; Trp Tryptophan; Tα1 Thymosin … For instance, thymosin α1, a naturally occurring thymic peptide, induces IDO expression, and immunosuppressive function of DCs, by stimulating TLR and IFN signaling [ 260 , 261 ]. Interestingly, the gut microbiota aids in tryptophan metabolism as well. …

Derivation and Characterization of Endothelial Cells from Porcine Induced Pluripotent Stem Cells.

Although the study on the regulatory mechanism of endothelial differentiation from the perspective of development provides references for endothelial cell (EC) derivation from pluripotent stem cells, incomplete reprogramming and donor-specific epigenetic memory are still thought to be the obstacles of iPSCs for clinical application. Thus, it is necessary to establish a stable iPSC-EC induction system and investigate the regulatory mechanism of endothelial differentiation. Based on a single-layer culture system, we successfully obtained ECs from porcine iPSCs (piPSCs). In vitro, the derived piP

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… Thymosin β4 promotes the survival and angiogenesis of transplanted endothelial progenitor cells in the infarcted myocardium Int. J. Mol. Med. 2017 39 1347 1356 10.3892/ijmm.2017.2950 28440414 PMC5428935 44. Park T.S. Bhutto I. Zimmerlin L. Huo J.S. Nagaria P. Miller D. Rufaihah A.J. Talbot C. …

A Review of Repurposed Cancer Drugs in Clinical Trials for Potential Treatment of COVID-19.

The pandemic of the coronavirus disease 2019 (COVID-19) represents an unprecedented challenge to identify effective drugs for prevention and treatment. While the world's attention is focused on news of COVID-19 vaccine updates, clinical management still requires improvement. Due to the similarity of cancer-induced inflammation, immune dysfunction, and coagulopathy to COVID-19, anticancer drugs, such as Interferon, Pembrolizumab or Bicalutamide, are already being tested in clinical trials for repurposing, alone or in combination. Given the rapid pace of scientific discovery and clinical data ge

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… folate dependent pathways leading to inhibition of DNA synthesis | France | NCT04481633 | Hydroxychloroquine | Recruiting | Not applicable | COVID-19 infection | Rate of patients with positive anti-COVID19 serology | [ 10 ] Nasal IFN-A1B | Jak1 and Tyk2 | Jak1 and Tyk2 | China | NCT04320238 | Anti-thymosin …

Correlation of long non-coding RNA expression with metastasis, drug resistance and clinical outcome in cancer.

The therapeutic response and clinical outcome of patients diagnosed with the same cancer type and that receive identical treatment is highly variable to reflect the genetic heterogeneity within tumor cells. Non-coding RNAs (ncRNAs) are recently discovered molecules that regulate eukaryotic gene expression and represent a significant advance towards a better understanding of the mechanisms that govern cellular growth. NcRNAs are essential for the proper regulation of cell proliferation and survival under physiologic conditions and are deregulated in many pathologies, e.g., human cancers. NcRNAs

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… reprograms chromatin state to promote cancer metastasis Nature 2010 464 7291 1071 1076 20393566 10.1038/nature08975 PMC3049919 90 Ji P Diederichs S Wang W Böing S Metzger R Schneider PM Tidow N Brandt B Buerger H Bulk E Thomas M Berdel WE Serve H Müller-Tidow C MALAT-1, a novel noncoding RNA, and thymosin …