Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-B activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferonalpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogenetargeted cancer therapy. (Blood. 2009; 113:6528-6532)

The emergence of the new coronavirus 2019 (COVID-19) was first seen in December 2019, which has spread rapidly and become a global pandemic. The number of cases of COVID-19 and its associated mortality have raised serious concerns worldwide. Early diagnosis of viral infection undoubtedly allows rapid intervention, disease management, and substantial control of the rapid spread of the disease. Currently, the standard approach for COVID-19 diagnosis globally is the RT-qPCR test; however, the limited access to kits and associated reagents, the need for specialized lab equipment, and the need for highly skilled personnel has led to a detection slowdown. Recently, the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic systems has reshaped molecular diagnosis. The benefits of the CRISPR system such as speed, precision, specificity, strength, efficiency, and versatility have inspired researchers to develop CRISPR-based diagnostic and therapeutic methods. With the global COVID-19 outbreak, different groups have begun to design and develop diagnostic and therapeutic programs based on the efficient CRISPR system. CRISPR-based COVID-19 diagnostic systems have advantages such as a high detection speed (i.e., 30 min from raw sample to reach a result), high sensitivity and precision, portability, and no need for specialized laboratory equipment. Here, we review contemporary studies on the detection of COVID-19 based on the CRISPR system.

BackgroundHTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN.ResultsHere we assessed Th1/Th2/Treg cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a Treg/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4+CD25+ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4+CD25+ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30.ConclusionsThe observed shift from a Treg/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.

Coronavirus 2019 (COVID-19), as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.

Highlights Convalescent plasma (CP) improves outcomes and decrease mortality rate in COVID-19. CP seems to be most beneficial for treating severe COVID-19 with mild ARDS. Early administration of CP could contribute to the treatment of severe COVID-19.

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Background: Candida albicans as an opportunistic fungus is one of the most important causes of late-onset morbidity and mortality in patients with major burns and severely impaired immune system. In recent years, the emergence of resistance to opportunistic fungi and toxicity of antimicrobial drugs make it necessary to develop new drugs. Methods: In the present study, we investigated anticandidal effects of indolicidin, as a representative of host defense peptide, conjugated with gold nanoparticles in fluconazole-resistant clinical isolates of C. albicans . After characterizing the conjugation of indolicidin using biophysical methodologies, the cytotoxicity and hemolytic activity of the nanocomplex were examined. In addition, the expression level of ERG11 , responsible for antifungal resistance, and the immunomodulatory effect of peptide-nanomaterial conjugates were assessed. Results: Our data indicated that the nanocomplex was nontoxic for the fibroblast cells and erythrocytes. Treatment with the nanocomplex significantly reduced the expression levels of the ERG11 gene in fluconazole-resistant C. albicans isolates and the iNOS gene in macrophages. Conclusion: The study data provides a chance to develop innovative therapies for the treatment of C. albicans burn infections. However, further investigation is required to examine the efficiency of the nanocomplex.

There are steps to achieve an optimum life for patients with hemophilia in developing countries, and awareness of the pattern of death in patients with hemophilia is a prerequisite for any health-care program. Owing to the lack of any data on the pattern of death in patients with hemophilia from developing countries, the current study was done to address common causes of death, and the spectrum of causes of death among individuals with hemophilia A and B. To address the pattern of death in northeast of Iran, we retrospectively collected demographic data regarding deceased patients with hemophilia A and B. Overall, among 379 people with hemophilia A and B, there were 46 deaths. Thirty-two deaths happened in the severe forms of the diseases. The obtained results show the patterns of death in the patients studied are not as parallel as some reports from the developed countries. Traumatic and spontaneous bleeding events were the main causes of death. The trend of death shows a decrease in the current decade post better therapeutic facilities. Evaluation of causes of death in hemophilia can be a useful indicator for managing the efficacy of health care in the current patients.