An extensive review on antifungal approaches in the treatment of mucormycosis

During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.     

Supramolecular platinum complexes for cancer therapy

The rise of supramolecular chemistry offers new tools to design therapeutics and delivery platforms for biomedical applications. This review aims to highlight the recent developments that harness host-guest interactions and self-assembly to design novel supramolecular Pt complexes as anticancer agents and drug delivery systems. These complexes range from small host-guest structures to large metallosupramolecules and nanoparticles. These supramolecular complexes integrate the biological properties of Pt compounds and novel supramolecular structures, which inspires new designs of anticancer approaches that overcome problems in conventional Pt drugs. Based on the differences in Pt cores and supramolecular structures, this review focuses on five different types of supramolecular Pt complexes, and they include host-guest complexes of the FDA-approved Pt(II) drugs, supramolecular complexes of nonclassical Pt(II) metallodrugs, supramolecular complexes of fatty acid-like Pt(IV) prodrugs, self-assembled nanotherapeutics of Pt(IV) prodrugs, and self-assembled Pt-based metallosupramolecules.     

Suppressive Effect of Liposomes Containing DNA Coding for Diphtheria Toxin A-Chain on Cells Transformed with Bovine Leukemia Virus

A recombinant plasmid which contained a gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) (BLV-LTR) was constructed to test a novel application of liposomes as antiviral agents. The promoter activity of BLV-LTR was estimated by the chloramphenicol acetyltransferase (CAT) assay using a plasmid which contains the coding sequence of CAT under the control of BLV-LTR (pBLVCAT). When BLV-infected cells were transfected with pBLVCAT, CAT activity was detected. BLV-uninfected cell lines, however, showed no detectable CAT activity. The plasmid DNA entrapped in liposomes was added to BLV-infected cells in culture. Syncytium formation induced by BLV-infected cells was effectively suppressed by the liposomes containing the gene for DT-A under the control of BLV-LTR. Conversely, liposomes containing the gene for DT-A without a promoter showed no such effect. DT-A gene-containing liposomes with BLV-LTR did not affect formation of syncytium induced by bovine immunodeficiency virus. These observations indicate that BLV-infected cells were readily targeted on the level of gene expression. This strategy could be applied to the treatment of BLV-induced B-cell proliferation of cattle, and further to other viral/neoplastic diseases where specific gene expression is exerted.     

基于益生菌治疗帕金森病的研究进展

帕金森病是常见的神经退行性疾病,其发病原因至今尚未明确,目前的治疗方法价格昂贵、效果差且副作用大。帕金森病患者常见胃肠道功能障碍,帕金森病和肠道菌群之间的关联已得到实验证实,患者有望通过益生菌改善肠道菌群达到治疗的目的。工程益生菌的出现使得人们可以按照自己的意愿改造益生菌,提高其稳定性和靶向性,展现出其特有的应用潜力。本文将从益生菌治疗帕金森病的研究现状出发,阐述益生菌治疗帕金森病的可能机制,进一步分析工程益生菌治疗帕金森病的可行性,为该疾病的安全治疗提供新的思路。     

PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target

Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy.     

Controlled release of adeno-associated virus from alginate hydrogel microbeads with enhanced sensitivity to ultrasound

Adeno-associated virus (AAV)-based gene therapy holds promise as a fundamental treatment for genetic disorders. For clinical applications, it is necessary to control AAV release timing to avoid an immune response to AAV. Here we propose an ultrasound (US)-triggered on-demand AAV release system using alginate hydrogel microbeads (AHMs) with a release enhancer. By using a centrifuge-based microdroplet shooting device, the AHMs encapsulating AAV with tungsten microparticles (W-MPs) are fabricated. Since W-MPs work as release enhancers, the AHMs have high sensitivity to the US with localized variation in acoustic impedance for improving the release of AAV. Furthermore, AHMs were coated with poly-l -lysine (PLL) to adjust the release of AAV. By applying US to the AAV encapsulating AHMs with W-MPs, the AAV was released on demand, and gene transfection to cells by AAV was confirmed without loss of AAV activity. This proposed US-triggered AAV release system expands methodological possibilities in gene therapy.     

Circadian Rhythm of Cardiac Output, Peripheral Vascular Resistance, and Related Variables by a Beat-to-Beat Monitoring

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.     

Comparación de los libros de historia de vida digitales y convencionales sobre el estado de ánimo,la comunicación,la cognición y la calidad de vida en personas con demencia en residencias: un estudio piloto

IntroductionPerson-centered care (PCC) includes life story, a form of reminiscence therapy that can be useful in the treatment of dementia. We compared the efficacy of using a digital or conventional life story book (LSB) on depressive symptoms, communication, cognition, and quality of life.Material and methodsThirty one persons with dementia living in 2 PCC nursing homes were randomly assigned to receive reminiscence therapy based on the Neural Actions digital LSB (n = 16) or a conventional LSB (n = 15). Both groups performed 2 weekly sessions of 45 min for 5 weeks. Depressive symptoms were evaluated with the Cornell scale (CSDD); communication with the Holden scale (HCS), cognition with the Mini Mental State Examination (MMSE) and quality of life with the quality of life scale for Alzheimer's (QoL-AD). The results were analyzed using ANOVA of repeated measures with the jamovi 2.3 program.ResultsBoth LSB improved communication skills (η² = 0.115; p < 0.001), with no differences between groups. No effects on quality of life, cognition, or mood were found.ConclusionsIn PCC centres digital or conventional LSB can be useful in the treatment of people with dementia by facilitating communication. Its role on quality of life, cognition or mood is uncertain.     

Long-term follow up of patients with common variable immunodeficiency treated with intravenous immunoglobulin: Reevaluation of intravenous immunoglobulin replacement therapy

Five patients with common variable immunodeficiency treated in our hospital between December 1979 and December 1990 were given six kinds of intravenous immunoglobulin preparations (pepsin treated, S-sulfonated, polyethylene glycol treated, pH4 treated, alkylated, and pH4.25 formulation preparation) for replacement therapy. Duration of the therapy ranged from 7.6 to 11 years. Incidences of fever and acute infections were variable among patients, but no significant differences were seen in the incidences among periods given each preparation. Three cases revealed abnormal pulmonary functions in tests. Adverse reactions were rarely seen in our study periods, and no severe reactions were observed. No significant differences were seen in incidences of adverse reactions. Postinfusion levels of serum complement slightly decreased from preinfusion levels. However, the decrease in complement was not related to any adverse reaction. No long-term complications such as transmission of hepatitis have been observed. Our data suggest that no obvious differences exist between the efficacy and safety of each IVIG preparation. Differences of efficacy of IVIG replacement therapy may be due to the variable pathophysiology of each patient.Abbreviations CVID common variable immunodeficiency - IVIG intravenous immunoglobulin     

Human pluripotent stem cell-derived extracellular vesicles: From now to the future

Extracellular vesicles (EVs) are nanometric particles that enclose cell-derived bioactive molecules in a lipid bilayer and serve as intercellular communication tools. Accordingly, in various biological contexts, EVs are reported to engage in immune modulation, senescence, and cell proliferation and differentiation. Therefore, EVs could be key elements for potential off-the-shelf cell-free therapy. Little has been studied regarding EVs derived from human pluripotent stem cells (hPSC-EVs), even though hPSCs offer good opportunities for induction of tissue regeneration and unlimited proliferative ability. In this review article, we provide an overview of studies using hPSC-EVs, focusing on identifying the conditions in which the cells are cultivated for the isolation of EVs, how they are characterized, and applications already demonstrated. The topics reported in this article highlight the incipient status of the studies in the field and the significance of hPSC-EVs’ prospective applications as PSC-derived cell-free therapy products.