Tissue Engineering and Regeneration of the Human Hair Follicle in Androgenetic Alopecia: Literature Review

Androgenetic alopecia (AGA) is an androgen-dependent process and represents the most frequent non-scarring alopecia. Treatments for AGA do not always achieve a satisfactory result for the patient, and sometimes cause side effects that lead to discontinuation of treatment. AGA therapeutics currently includes topical and oral drugs, as well as follicular unit micro-transplantation techniques. Tissue engineering (TE) is postulated as one of the possible future solutions to the problem and aims to develop fully functional hair follicles that maintain their cyclic rhythm in a physiological manner. However, despite its great potential, reconstitution of fully functional hair follicles is still a challenge to overcome and the knowledge gained of the key processes in hair follicle morphogenesis and biology has not yet been translated into effective replacement therapies in clinical practice. To achieve this, it is necessary to research and develop new approaches, techniques and biomaterials. In this review, present and emerging hair follicle bioengineering strategies are evaluated. The current problems of these bioengineering techniques are discussed, as well as the advantages and disadvantages, and the future prospects for the field of TE and successful hair follicle regeneration.

Putative Secondary Structure at 5’UTR as a Potential Antiviral Target against SARS-CoV-2

SARS-CoV-2 is an enveloped positive-sense single-stranded RNA coronavirus that causes COVID-19, of which the current outbreak has resulted in a high number of cases and fatalities throughout the world, even vaccine doses are being administered. The aim of this work was to scan the SARS-CoV-2 genome in search for therapeutic targets. We found a sequence in the 5’UTR (NC 045512:74-130), consisting of a typical heptamer next to a structured region that may cause ribosomal frameshifting. The potential biological value of this region is relevant through its low similarity with other viruses, including coronaviruses related to SARS-CoV, and its high sequence conservation within multiple SARS-CoV-2 isolates. We have predicted the secondary structure of the region by means of different bioinformatic tools. We have suggested a most probable secondary structure to proceed with a 3D reconstruction of the structured segment. Finally, we carried out virtual docking on the 3D structure to look for a binding site and then for drug ligands from a database of lead compounds. Several molecules that could be probably administered as oral drugs show promising binding affinity within the structured region, and so it could be possible interfere its potential regulatory role.

Managing the Unpredictable: Mechanistic Analysis and Clinical Recommendations for Lamotrigine Treatment after Bariatric Surgery

Bariatric surgery may alter the absorption and overall bioavailability of oral drugs. Lamotrigine is a major antiepileptic and mood stabilizer, that its use after bariatric surgery has not yet been studied. In this article, we provide a thorough mechanistic analysis of the effects of bariatric surgery on multiple mechanisms important for the absorption, bioavailability and overall pharmacokinetics of lamotrigine. Attributable to its pharmacokinetic properties and drug characteristics, the use of lamotrigine after bariatric surgery may be challenging. The complex situation in which some mechanisms may lead to increased drug exposure (e.g., decreased metabolism, weight loss) while others to its decrease (e.g., hampered dissolution/solubility, decreased gastric volume), may result in lowered, unchanged, or enhanced lamotrigine plasma levels after the surgery. We conclude with a set of clinical recommendations for lamotrigine treatment after bariatric surgery, aiming to allow better patient care, and emphasizing the extra caution that needs to be taken with these patients.

Oral Versus Intravenous Chemotherapy in COVID-19 Epidemic

The novel coronavirus has a significant impact on the routine clinical practice for cancer patients in China since December 2019. During the epidemic in mainland China, especially Wuhan, the intravenous chemotherapies of cancer patients were considerably delayed. Up to now, cancer patients throughout the world directly encounter similar obstacles. For patients who have the right to choose chemotherapeutic regimens with different administration routes, oral drugs can be considered to be applied. In this mini-review, oral chemotherapeutic drugs were compared with intravenous drugs in seven types of tumors. Accordingly, we intended to provide useful suggestions for clinicians to balance the benefits and risks of oral against intravenous chemotherapies and to choose properly substituted oral chemotherapeutic regimens for cancer patients amid the coronavirus disease 2019 (COVID-19) pandemic.

Incorporating patient preferences into osteoarthritis treatment

Objectives: This study aims to identify the relationship between treatment modalities and the patients’ preferences in osteoarthritis (OA) treatment and identify the related factors. Patients and methods: This multi-center, cross-sectional study included a total of 305 patients with OA (66 males, 239 females; mean age: 66.4±9.7 years; range, 38 to 90 years) between July 2019 and January 2020. Data including demographic and clinical characteristics of the patients were recorded using a structured questionnaire. Results: The mostly common involvement sites were knee joints, lumbar, and cervical regions, respectively. Prior to the study, the treatment modalities which were prescribed to patients were oral drugs (79.7%), topical drugs (73.8%), home-based exercise program (62.6%), and physical therapy (outpatient) (61.3%). Of the recommended remedy, 89.2% were prescribed by physiatrists, 24.6% by orthopedists, 5.6% by family practitioners, 2.6% by neurosurgeons, and 1.6% by algologists. The most beneficial treatments (to whom) were inpatient physical therapy program (47%), oral drugs (41%), home-based exercise programs (24.9%) according to patients’ perspective. According to patient preferences, nearly half of the patients preferred outpatient physical therapy program (45.9%), oral drugs (33.1%), inpatient physical therapy (20%), and home-based exercises (18%). The most common reasons for their preferences were previous benefits from treatment (54.4%), long-term effects (38%), easy access to treatment (33.1%) and concerns about side effects (28.9%). The mostly common reasons for their preferences were previous benefits from the treatment (54.4%), long-term positive effects of physical therapy (38%), easy access to the treatment (33.1%) and concerns about side effects of drugs (28.9%). Conclusion: Besides medical regimen, the results of this study showed that the patients preferred outpatient and inpatient physical therapy modalities, and home-based exercises programs. In the light of these findings, initiation of a new prescription (e.g., drugs or physical therapy modalities) in OA patients, previous treatment modalities, and approaches are suggested to be carefully reviewed by the clinician to anticipate and improve the adherence behavior to the new treatment.

Oral Lipid-Lowering Treatments Beyond Statins: Too Old and Outdated or Still Useful?

Purpose of Review For many years, the lipid-lowering armamentarium consisted of statins and/or ezetimibe and/or bile acid sequestrants and/or fibrates. Now, with the availability of new drugs mostly injectables, the field has changed and the role of oral non-statin drugs (including bempedoic acid) must be reevaluated. Recent Findings Ezetimibe remains a very important combination partner for statins with continuously increasing treatment numbers. Bempedoic acid is another interesting combination partner for statin/ezetimibe or ezetimibe alone but lacks in contrast to ezetimibe evidence from outcome trials. The role of fibrates is less clear as they have shown disappointing results in outcome trials but may still be used in selected, high-risk patients with combined dyslipidemia. Bile acid sequestrants are now rarely used as there are stronger, better tolerable ways to lower LDL-cholesterol. Summary With the introduction of new injectable lipid-lowering drugs, some oral drugs such as ezetimibe and bempedoic acid still have an important spot in our treatment algorithm others such as fibrates have a less clear role while again others are now rarely used.

Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy

Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE.Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE.Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02–1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12–2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18–1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54–1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54–0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients.Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.

Multifunctional Small Molecules as Potential Anti-Alzheimer’s Disease Agents

Alzheimer’s disease (AD) is a severe multifactorial neurodegenerative disorder characterized by a progressive loss of neurons in the brain. Despite research efforts, the pathogenesis and mechanism of AD progression are not yet completely understood. There are only a few symptomatic drugs approved for the treatment of AD. The multifactorial character of AD suggests that it is important to develop molecules able to target the numerous pathological mechanisms associated with the disease. Thus, in the context of the worldwide recognized interest of multifunctional ligand therapy, we report herein the synthesis, characterization, physicochemical and biological evaluation of a set of five (1a–e) new ferulic acid-based hybrid compounds, namely feroyl-benzyloxyamidic derivatives enclosing different substituent groups, as potential anti-Alzheimer’s disease agents. These hybrids can keep both the radical scavenging activity and metal chelation capacity of the naturally occurring ferulic acid scaffold, presenting also good/mild capacity for inhibition of self-Aβ aggregation and fairly good inhibition of Cu-induced Aβ aggregation. The predicted pharmacokinetic properties point towards good absorption, comparable to known oral drugs.

Overlapping effects of miR-21 inhibition and drugs for idiopathic pulmonary fibrosis in the post-myocardial infarction setting

Background Intracoronary infusion of a specific miR-21 inhibitor after reperfused MI has been reported to reduce cardiac fibrosis and hypertrophy and improve cardiac function in pigs. Possible drawbacks of anti-miR-21 therapy are the high costs of this therapy, and the need for intracoronary administration, preferably some days after reperfusion. Oral drugs with anti-fibrotic actions could have similar effects than anti-miR-21, while overcoming the limitations of anti-miR-21. We tested this hypothesis by examining the two oral drugs approved for idiopathic pulmonary fibrosis (nintedanib and pirfenidone). Methods We identified the regulatory profile of miR-21, which included 588 target genes. Only 99 of these interactions were supported by information from reporter gene assays. The biological significance of these 99 targets was evaluated through over-representation analysis, and 13 genes were identified as potentially related to cardiovascular diseases. We retrieved all known targets and main downstream interactions of nintedanib and pirfenidone from Drugbank. Finally, we cross-validated these datasets by using neural network analyses to search for protein-protein interactions, focusing on those shared by miR-21 inhibition, nintedanib and pirfenidone. Results Nintedanib and anti-miR21 had many targets in common, which could indicate an overlap in their corresponding mechanisms of action. The proto-oncogene SRC, which participates in gene transcription, immune response, apoptosis and migration, emerged as the leading signaling effector. By blocking SRC expression and many downstream effectors of SRC, as well as platelet-derived growth factor, nintedanib could decreased miR-21 expression. The molecular effects of nintedanib include inhibition of inflammation, fibrosis and angiogenesis, and then ultimately a relief from I/R injury, in a similar fashion than anti-miR-21. Contrary to nintedanib, no overlap between the effects of pirfenidone and anti-miR-21 was found. Conclusion Because of the remarkably strong overlapping with the targets of miR-21, there is a stronger rationale to assess nintedanib than pirfenidone as a cardioprotective therapy. If confirmed by experimental evidence, nintedanib could enter the stage of clinical trials to assess its efficacy in human patients with STEMI. Funding Acknowledgement Type of funding sources: None.