The Macrophages-Microbiota Interplay in Colorectal Cancer (CRC)-Related Inflammation: Prognostic and Therapeutic Significance

Tumor-associated macrophages (TAMs) are the main population of myeloid cells infiltrating solid tumors and the pivotal orchestrators of cancer-promoting inflammation. However, due to their exceptional plasticity, macrophages can be also key effector cells and powerful activators of adaptive anti-tumor immunity. This functional heterogeneity is emerging in human tumors, colorectal cancer (CRC) in particular, where the dynamic co-existence of different macrophage subtypes influences tumor development, outcome, and response to therapies. Intestinal macrophages are in close interaction with enteric microbiota, which contributes to carcinogenesis and affects treatment outcomes. This interplay may be particularly relevant in CRC, one of the most prevalent and lethal cancer types in the world. Therefore, both macrophages and intestinal microbiota are considered promising prognostic indicators and valuable targets for new therapeutic approaches. Here, we discuss the current understanding of the molecular circuits underlying the interplay between macrophages and microbiota in CRC development, progression, and response to both conventional therapies and immunotherapies

Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma

Ribonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m2, with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients’ survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists

Recent Advances in Biomedical, Therapeutic and Pharmaceutical Applications of Microbial Surfactants

The spread of antimicrobial-resistant pathogens typically existing in biofilm formation and the recent COVID-19 pandemic, although unrelated phenomena, have demonstrated the urgent need for methods to combat such increasing threats. New avenues of research for natural molecules with desirable properties to alleviate this situation have, therefore, been expanding. Biosurfactants comprise a group of unique and varied amphiphilic molecules of microbial origin capable of inter-acting with lipidic membranes/components of microorganisms and altering their physicochemical properties. These features have encouraged closer investigations of these microbial metabolites as new pharmaceutics with potential applications in clinical, hygiene and therapeutic fields. Mounting evidence has indicated that biosurfactants have antimicrobial, antibiofilm, antiviral, immunomodu-latory and antiproliferative activities that are exploitable in new anticancer treatments and wound healing applications. Some biosurfactants have already been approved for use in clinical, food and environmental fields, while others are currently under investigation and development as antimicrobials or adjuvants to antibiotics for microbial suppression and biofilm eradication strategies. Moreover, due to the COVID-19 pandemic, biosurfactants are now being explored as an alternative to current products or procedures for effective cleaning and handwash formulations, antiviral plastic and fabric surface coating agents for shields and masks. In addition, biosurfactants have shown promise as drug delivery systems and in the medicinal relief of symptoms associated with SARS-CoV-2 acute respiratory distress syndrome

Cholesterol impairment contributes to neuroserpin aggregation

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer's and Parkinson's diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol regulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.Comment: 7 figure

Renal cell carcinoma and viral infections: A dangerous relationship?

: Virus-related cancers in humans are widely recognized, but in the case of renal cancer, the link with the world of viruses is not clearly established in humans, despite being known in animal biology. In the present review, we aimed to explore the literature on renal cell carcinoma (RCC) for a possible role of viruses in human RCC tumorigenesis and immune homeostasis, hypothesizing the contribution of viruses to the immunogenicity of this tumor. A scientific literature search was conducted using the PubMed, Web of Science, and Google Scholar databases with the keywords "virus" or "viruses" or "viral infection" matched with ("AND") "renal cell carcinoma" or "kidney cancer" or "renal cancer" or "renal carcinoma" or "renal tumor" or "RCC". The retrieved findings evidenced two main aspects testifying to the relationship between RCC and viruses: The presence of viruses within the tumor, especially in non-clear cell RCC cases, and RCC occurrence in cases with pre-existing chronic viral infections. Some retrieved translational and clinical data suggest the possible contribution of viruses, particularly Epstein-Barr virus, to the marked immunogenicity of sarcomatoid RCC. In addition, it was revealed the possible role of endogenous retrovirus reactivation in RCC oncogenesis, introducing new fascinating hypotheses about this tumor's immunogenicity and likeliness of response to immune checkpoint inhibitors

Quantitative Characterization of Gait Patterns in Individuals with Spinocerebellar Ataxia 38

Spinocerebellar ataxia 38 (SCA 38) is a rare autosomal neurological disease whose clinical features include, among others, severe gait disturbances that have not yet been fully characterized. In this study, we employed a computerized 3D gait analysis to obtain spatio-temporal parameters of gait and the kinematics in the sagittal plane in the hip, knee, and ankle joints of seven individuals with SCA 38, which were then compared with those of twenty unaffected individuals matched for age, sex, and anthropometric features. The results show that, in comparison with unaffected individuals, those with SCA 38 are characterized by a significantly reduced speed, stride length, and duration of the swing phase, as well as an increased step width and stance and double support phase durations. The point-by-point comparison of the angular trends at the hip, knee, and ankle joints revealed significant alterations during most part of the stance phase for hip joint and at pre-swing/swing phases for knee and ankle joints. For these latter joints, a significantly reduced dynamic range of motion was also found. Such findings provide some new insights into hip and knee kinematics for this specific form of ataxia and may be useful for monitoring the disease’s progression and designing specific, tailored rehabilitative interventions

Immunological Effects of Multikinase Inhibitors for Kidney Cancer: A Clue for Integration with Cellular Therapies?

The multikinase inhibitors Sunitinib and Sorafenib not only inhibit angiogenesis and tumor growth, but also have the potential of interacting with the function of the immune system