Associated Bacterial Coinfections in COVID-19-Positive Patients.

Background and Objectives: The aim of this study was to identify specific rhino- and oropharyngeal microbiological pathogens as well as associated comorbidities that favor SARS-CoV-2 infection and corelate them. Materials and Methods: This prospective clinical study enrolled 61 patients (28 COVID-19-positive and 33 controls) who were tested for other comorbidities and co-existence of associated oral pathogenic microbiota. Results: A total of 247 bacterial isolates were identified in the bacterial cultures in both groups. Viral hepatitis type A was more prevalent in the COVID-19-positive group (p = 0.026), as was the presence of oral candidiasis (p = 0.006). In the control group, a moderate direct relationship was observed between the Beta hemolytic streptococcus group G and dermatitis, and strong direct relationships were observed between the Beta hemolytic streptococcus group G and external otitis, Streptococcus pyogenes and dental alveolitis, and Streptococcus pyogenes and chronic lymphocytic leukemia. In the test group, strong direct relationships were observed between Hemophilus influenzae and pulmonary thromboembolism; Staphylococcus aureus and autoimmune thyroiditis; post-viral immunosuppression, chronic coronary syndrome, and hypernatremia; Beta hemolytic streptococcus group C and rheumatoid polyneuropathy; Beta hemolytic streptococcus group G and hyperkalemia, hypothyroidism, secondary anemia, and splenomegaly; and active oral candidiasis and SARS-CoV-2 viral pneumonia. The following relationships were strong, but inverse: Beta hemolytic streptococcus group G and acute respiratory failure, and active oral candidiasis and SARS-CoV-2 viral bronchopneumonia. Conclusions: Briefly, COVID-19-positive patients have the predisposition to build up associated comorbidities and coinfections, which can be the expression of the immune burden that this virus generates to the host.

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis.

Background and Objectives: The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity; thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods: The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results: ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity; thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions: The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact.

Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity.

Betulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome these drawbacks, numerous strategies were conducted to improve its physicochemical and pharmacokinetic profile, among which cocrystalization emerged as a promising approach. Thus, our work consisted in obtaining slowly grown cocrystals of BA and ascorbic acid (BA+VitC) in isopropyl alcohol obtained in a hydrothermal experiment. The newly formed cocrystals were characterized by physico-chemical methods such asSEM, DSC, XRPD, and FT-IR spectroscopy demonstrating BA+VitC cocrystal formation while their antioxidant activity revealed an additive antioxidant effect. To investigate the biological effect, BA+VitC cocrystals were tested on HaCat (immortalized human keratinocytes), B164A5 and B16F0 (murine melanoma), MCF7 and MDA-MB-231 (human breast cancer), and HeLa (cervical cancer) cell lines. Results of BA upon the tested tumor cell lines, after co-crystallization with vitamin C, indicated a superior cytotoxic effect with the preservation of a good selectivity index assumably due to an improved BA water solubility and consequently an optimized bioavailability.

The characterization of PDGFR-alpha and PDGFR-beta expression in malignant non-Hodgkin lymphoma.

PDGF receptors play an important role in tumor progression as being part of a group of receptors that are expressed along the membrane of tumor cells. The aim of this study was to evaluate the PDGF receptor expression in follicular and diffuse forms of non-Hodgkin malignant lymphoma. We evaluated 38 biopsy fragments from patients diagnosed with malignant non-Hodgkin lymphoma. We noticed the distribution of PDGFR-alpha and -beta in tumor cells and the immunoreactivity was quantified as the percentage of positive tumor cells. We noticed the presence of score 3, more than 30% of tumor cells positive, for PDGFR-alpha and PDGFR-beta in 50% and 75% cases of follicular non-Hodgkin lymphoma. For diffuse malignant non-Hodgkin lymphomas, score 3 was noted in 23.52% of cases for PDGFR-alpha and 35.29% of cases for PDGFR-beta. This may represent an important therapeutic target in patients who do not respond to conventional therapy, but further research is needed for a careful evaluation of benefits and side effects of PDGFR inhibitors.

Heterogeneity of malignant non-Hodgkin lymphoma-associated blood vessels.

The present study described for the first time a high heterogeneity of blood vessels in non-Hodgkin lymphomas (nHL). The tumor blood vessels were highlighted with CD105÷smooth muscle actin (SMA) and CD34/SMA double immunostaining. For both follicular and diffuse types of lymphomas, more than 85% of CD34/SMA positive vessels were of immature and intermediate type. A percent of 96.54 from CD105/SMA assessed blood vessels were of activated and mature activated types with high expression of CD105 on endothelial cells of newly formed blood vessels. Our results suggest that these types of vessels are potential therapeutic targets for antivascular therapy.

Mast cells contribute to the angiogenesis in non-Hodgkin lymphoma. An immunohistochemical study based on the relationship with microvessel density.

Only few data are available in the literature concerning angiogenesis in hematological malignancies. Non-Hodgkin lymphoma classified on the base of molecular profile is frequently characterized by unpredictable behavior that seems to be related to tumor cells and also to the tumor microenvironment. The tumor microenvironment contains blood vessels and a large variety of cells that can play an important role to the progression of angiogenesis and tumor growth. From these, mast cells have been shown to be a source of angiogenic factors. The aim of this work was to investigated the relationships between mast cells and blood vessels in non-Hodgkin lymphoma and reactive lymphoid tissue from three different anatomical sites. Using double immunostaining method CD34/mast cell tryptase we noticed that mast cell density was significantly lower in the follicular lymphoma than in diffuse type lymphoma. The morphology of vessels, the presence of pillars and splitting suggested that intussusceptions is the main mechanism of angiogenesis. In the cases with primary lymphoma of the spleen, we found few mast cells and a high number of blood vessels. Our data suggest that lymphoma-associated angiogenesis is driven in part by the tumor microenvironment, and particularly, by mast cells. On the other hand, our results support the organ-specific tumor-associated angiogenesis in malignant non-Hodgkin lymphoma.