Compatibility of Different Formulations in Pentravan® and Pentravan® Plus for Transdermal Drug Delivery

The potential therapeutic benefit of transdermal delivery systems for some active pharmaceutical ingredients (APIs) has been well-established for decades within the scientific community. However, together with the clinical efficacy, there is the need for an evaluation of the stability of such APIs in bases with known transdermal capabilities, which is necessary to provide the compounding pharmacist with confidence when providing transdermal products. In this study, the stability of danazol, metformin HCl, and resveratrol as individual ingredients, as well as metformin HCl, resveratrol, and Vitamin D3 in combinations at bracketed high and low concentrations, were evaluated over a period of 6 months, using a ready-to-use transdermal vehicle for compounding pharmacies (Pentravan® or Pentravan® Plus). The five formulations tested (F1: Danazol 50 mg/g + MiodesinTM 85 mg/g in Pentravan®, F2: Metformin HCl 200 mg/g in Pentravan®, F3: Resveratrol 200 mg/g in Pentravan®, F4: Metformin HCl 100 mg/g + Resveratrol 100 mg/g + Vitamin D3 5000 IU in Pentravan®, and F5: Metformin HCl 200 mg/g + Resveratrol 200 mg/g + Vitamin D3 5000 IU in Pentravan® Plus) presented a beyond-use date of at least 6 months, presenting high convenience for the compounding pharmacies.

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

Interleukin-22 (IL-22), a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The potential therapeutic benefit of IL-22 is expected to be exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and a non-functional dimer. Monomeric IL-22 (mIL-22) was highly purified through a series of three separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate signal transducer and activator of transcription 3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

Ferroptosis: A Trusted Ally in Combating Drug Resistance in Cancer

: Ferroptosis, which is an iron-dependent, non-apoptotic cell death mechanism, has recently been proposed as a novel approach in cancer treatment. Bearing distinctive features and its exclusive mechanism have put forward the potential therapeutic benefit of triggering this newly discovered form of cell death. Numerous studies have indicated that apoptotic pathways are often deactivated in resistant cells, leading to a failure in therapy. Hence, alternative strategies to promote cell death are required. Mounting evidence suggests that drug-resistant cancer cells are particularly sensitive to ferroptosis. Given that cancer cells consume a higher amount of iron than healthy ones, ferroptosis not only stands as an excellent alternative to trigger cell death and reverse drug-resistance, but also provides selectivity in therapy. This review focuses specifically on overcoming drug-resistance in cancer through activating ferroptotic pathways and brings together the relevant chemotherapeutics-based and nanotherapeutics-based studies to offer a perspective for researchers regarding the potential use of this mechanism in developing novel therapeutic strategies.

Drugs intervention study in COVID-19 management

By 9 February 2021, the Coronavirus has killed 2,336,650 people worldwide and it has been predicted that this number continues to increase in year 2021. The study aimed to identify therapeutic approaches and drugs that can potentially be used as interventions in Coronavirus 2019 (COVID-19) management. A systematic scoping review was conducted. Articles reporting clinical evidence of therapeutic management of COVID-19 were selected from three different research databases (Google Scholar, PubMed, and Science Direct). From the database search, 31 articles were selected based on the study inclusion and exclusion criteria. This review paper showed that remdesivir and ivermectin significantly reduced viral ribonucleic acid (RNA) activity. On the other hand, convalescent plasma (CP) significantly improved COVID-19 clinical symptoms. Additionally, the use of corticosteroid increased survival rates in COVID-19 patients with acute respiratory distress syndrome (ARDS). Findings also indicated that both hydroxychloroquine and favipiravir were effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, lopinavir–ritonavir combination was not effective against COVID-19. Finally, ribavirin, galidesivir, and sofosbuvir showed potential therapeutic benefit in treating COVID-19, but there is a lack of clinical evidence on their effectiveness against SARS-CoV-2. Remdesivir, ivermectin, favipiravir, hydroxychloroquine, dexamethasone, methylprednisolone, and CP are the therapeutic agents that can potentially be used in COVID-19 management.

Case Report: Feasibility of a Novel Virtual Reality-Based Intervention for Patients With Schizophrenia

Schizophrenia is a severe and disabling mental illness, associated with persistent difficulties in social functioning. While gaining and retaining a job or staying socially integrated can be very difficult for the patients, the treatment of poor functionality remains challenging with limited options in pharmacotherapy. To address the limitations of medical treatment, several interesting and innovative approaches have been introduced in the field of psychotherapy. Recent approaches incorporate modern technology as well, such as virtual reality. A potential therapeutic benefit of virtual reality is particularly significant when an interpersonal dimension of the problem needs to be addressed. One example is a Virtual Reality based Theory of Mind Intervention (VR-ToMIS), a novel method, which enables patients to practice complex social interactions without the burden of real-life consequences. Our paper presents a case report showing promising results of VR-ToMIS. Ms. Smith is a 50- year-old patient who has been suffering from schizophrenia for 20 years. Although in her case there was no problem with compliance throughout the years, she had severe problems regarding social functionality. With VR-ToMIS, she improved in ToM and communicative-pragmatic skills. The effects of the intervention went beyond the increased scores of the tests. Before the intervention there was a risk of the patient becoming unemployed as she was unable to follow the main principles of communicative exchange. Usually, her contribution was more informative than was required. After the intervention her communication became more balanced and she could retain her job. This case suggests that VR-ToMIS may be a promising tool for treating social disfunction in schizophrenia.

Prognosticating role of serum eosinophils on immunotherapy efficacy in patients with advanced melanoma

Aim: To evaluate serum eosinophilia (≥500 peripheral eosinophil counts/microliter) in prognosticating immunotherapy (IO) efficacy. Methodology: A retrospective study of 86 patients with advanced melanoma on PD-1 inhibitors. Results: Eosinophilia-on-IO was an independent prognosticating factor for median OS (HR :0.223; 95% CI: 0.088–0.567; p = 0.002). ‘Late eosinophilia’ (≥1 year from IO start date) group had better median OS (31.9 vs 24.1 vs 13.0 months; p = 0.002) when compared with ‘early eosinophilia’ (<1 year from IO start date) and ‘no eosinophilia’ groups, respectively. Conclusion: Eosinophilia-on-IO and its timing were associated with better IO efficacy in patients with advanced melanoma. Our findings provided insights on potential therapeutic benefit of inducing eosinophilia at certain interval time to obtain a longer durable immunotherapy response.

The Development of Integrin Alpha-8 Deficient Lungs Shows Reduced and Altered Branching and a Correction of the Phenotype During Alveolarization

Lung development involves epithelial–mesenchymal interactions and integrins represent one of the key elements. These extracellular matrix receptors form hetero-dimers of alpha and beta subunits. The integrin α8β1 is highly expressed in mouse tissues, including lung. It forms a cellular receptor for fibronectin, vitronectin, osteopontin, nephronectin, and tenascin-C. This study aims to investigate the role of the integrin α8-subunit (α8) during lung development. Wild type and α8-deficient lungs were explanted at embryonic days 11.5/12.5. After 24–73 h in culture α8-deficient lung explants displayed reduced growth, reduced branching, enlarged endbuds, altered branching patterns, and faster spontaneous contractions of the airways as compared to wild type. Postnatally, a stereological investigation revealed that lung volume, alveolar surface area, and the length of the free septal edge were significantly reduced in α8-deficient lungs at postnatal days P4 and P7. An increased formation of new septa in α8-deficient lungs rescued the phenotype. At day P90 α8-deficient lungs were comparable to wild type. We conclude that α8β1 takes not only part in the control of branching, but also possesses a morphogenic effect on the pattern and size of the future airways. Furthermore, we conclude that the phenotype observed at day P4 is caused by reduced branching and is rescued by a pronounced formation of the new septa throughout alveolarization. More studies are needed to understand the mechanism responsible for the formation of new septa in the absence of α8β1 in order to be of potential therapeutic benefit for patients suffering from structural lung diseases.

Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review

The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women’s health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women’s cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.