Author Correction: Identification of PTGR2 inhibitors as a new therapeutic strategy for diabetes and obesity

Disclaimer. The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by high metabolic activity, chronic endoplasmic reticulum stress, and persistent redox imbalance. Excessive immunoglobulin synthesis and adaptation to the hypoxic bone marrow microenvironment lead to sustained production of reactive oxygen species (ROS). Their excessive accumulation promotes genomic instability, disease progression, osteolytic bone disease, and resistance to therapy. Paradoxically, MM cells adapt to oxidative stress by activating antioxidant and metabolic defense mechanisms, including Nuclear factor erythroid 2-related factor 2 (NRF2)- and Heme Oxygenase 1 (HMOX1)-dependent pathways, metabolic reprogramming, and overexpression of ROS-scavenging enzymes such as peroxiredoxin 6 (PRDX6), allowing survival at the threshold of oxidative toxicity. Evidence indicates that biomarkers of oxidative stress-such as lipid and protein oxidation products, antioxidant enzyme activity, and the Oxidative Stress Score-correlate with disease stage, prognosis, and treatment response. Redox-modulating therapeutic strategies, including pharmacological ROS induction, inhibition of antioxidant defenses, and the use of natural pro-oxidant compounds, are emerging as promising adjuncts to standard MM therapies. Recent studies also highlight the gut microbiota as an indirect regulator of oxidative balance, immune modulation, and metabolic homeostasis in MM. This review summarizes current knowledge on oxidative stress in multiple myeloma, emphasizing its role in pathogenesis, drug resistance, biomarker development, and emerging therapeutic and supportive strategies.

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Disclaimer. The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guide-lines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Despite controversy over the indications of couple therapy for IPV, current research has indicated some benefits. This article examines some crucial aspects when dealing with couple therapy for IPV, such as how dominance and power abuse are present, and which important issues should be taken into account during the therapeutic process and be brought up in therapeutic conversations. It also proposes strategies for therapists conducting couple therapy for IPV. Ten studies conducted within the Jyväskylä research project on couple therapy for IPV were reviewed. Findings highlighted the importance of the therapists’ awareness of the presence of violence, dominance and power during the sessions, and of how cultural issues could prevent their recognition. Responsibility and couple agreement on the violent behaviour seemed especially relevant at the beginning of the treatment. Potentially useful therapeutic strategies are directedness, use of reflective dialogue, and continuous assessment.Practitioner points In couple treatment for IPV therapists should (a) actively bring up violence, responsibility and parenting, and (b) reflect on the culturally dominant understandings of IPV To regulate the presence of dominance, therapists’ directivity might promote equal distribution of talk, and increase the therapeutic alliance Therapist strategies such as multivoiced addresses, reflective dialogue and a directive approach may promote clients’ responsibility and reflexivity

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, the growth of new capillaries from existing microvasculature. In peripheral arterial disease (PAD), lower extremity muscle ischemia develops downstream of atherosclerotic obstruction. A working hypothesis proposed that the maladaptive overexpression of soluble VEGF receptor 1 (sVEGFR1) in ischemic muscle tissues, and its subsequent antagonism of VEGF bioactivity, may contribute to the deficient angiogenic response in PAD, as well as the limited success of therapeutic angiogenesis strategies where exogenous VEGF genes/proteins are delivered. The objectives of this study were to develop a computational framework for simulating the systemic distributions of VEGF and sVEGFR1 (e.g., intramuscular vs. circulating, free vs. complexed) as observed in human PAD patients and to serve as a platform for the systematic optimization of diagnostic tools and therapeutic strategies. A three-compartment model was constructed, dividing the human body into the ischemic calf muscle, blood, and the rest of the body, connected through macromolecular biotransport processes. Detailed molecular interactions between VEGF, sVEGFR1, endothelial surface receptors (VEGFR1, VEGFR2, NRP1), and interstitial matrix sites were modeled. Our simulation results did not support a simultaneous decrease in plasma sVEGFR1 during PAD-associated elevations in plasma VEGF reported in literature. Furthermore, despite the overexpression in sVEGFR1, our PAD control demonstrated increased proangiogenic signaling complex formation, relative to our previous healthy control, due to sizeable upregulations in VEGFR2 and VEGF expression, thus leaving open the possibility that impaired angiogenesis in PAD may be rooted in signaling pathway disruptions downstream of ligand-receptor binding.

Under pathological conditions such as multiple sclerosis (MS), leukocytes infiltrate the central nervous system where they, in concert with activated microglia, promote inflammatory demyelination resulting in a broad spectrum of symptoms, including paralysis. Therefore, all current therapeutic approaches to MS target the immune system, blocking inflammation and paralysis progression, but may compromise the immune system. In this focused review, we present an underestimated compartment, the blood–brain barrier, which is compromised during MS and becomes permeable to leukocytes infiltrating the central nervous system. This barrier has the potential to offer new therapeutic strategies and is easily accessible for drugs. We highlight this paradigm using the example of the therapeutic anti-Reelin strategy we have developed. Reelin is a plasma protein that regulates the expression of adhesion markers on the endothelial surface, thus promoting the infiltration of inflammatory cells and propagating inflammation. Building Back a Better Blood–Brain Barrier (the “6B” strategy) may have advantages compared to actual immunosuppressive drugs because it restores a physiological function rather than suppressing the immune system.

Colorectal cancer (CRC) is one of the most common tumors worldwide, with a higher rate of distant metastases than other malignancies and with regular occurrence of drug resistance. Therefore, scientists are forced to further develop novel and innovative therapeutic treatment strategies, whereby it has been discovered microorganisms, albeit linked to CRC pathogenesis, are able to act as highly selective CRC treatment agents. Consequently, researchers are increasingly focusing on bacteriotherapy as a novel therapeutic strategy with less or no side effects compared to standard cancer treatment methods. With multiple successful trials making use of various bacteria-associated mechanisms, bacteriotherapy in cancer treatment is on its way to become a promising tool in CRC targeting therapy. In this study, we describe the anti-cancer effects of bacterial therapy focusing on the treatment of CRC as well as diverse modulatory mechanisms and techniques that bacteriotherapy offers such as bacterial-related biotherapeutics including peptides, toxins, bacteriocins or the use of bacterial carriers and underlying molecular processes to target colorectal tumors.

Breast cancer is one of the most prevalent malignant tumors among women and ranks as the second leading cause of cancer-related deaths in females, primarily due to delays in diagnosis and shortcomings in treatment strategies. Consequently, there is a pressing need to identify reliable therapeutic targets and strategies. In recent years, the identification of effective biomarkers-particularly novel molecular therapeutic targets-has become a focal point in breast cancer research, aimed at predicting disease aggressiveness and monitoring treatment responses. Simultaneously, advancements in understanding the molecular mechanisms underlying cellular programmed death have opened new avenues for targeting kinase-regulated programmed cell death as a viable therapeutic strategy. This review summarizes the latest research progress regarding kinase-regulated programmed death (including apoptosis, pyroptosis, autophagy, necroptosis, and ferroptosis) in breast cancer treatment. It covers the key kinases involved in this mechanism, their roles in the onset and progression of breast cancer, and strategies for modulating these kinases through pharmacological interventions.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents an urgent need for an effective vaccine. Molecular characterization of SARS-CoV-2 is critical to the development of effective vaccine and therapeutic strategies. In the present study, we show that the fusion of the SARS-CoV-2 spike protein receptor-binding domain to its transmembrane domain is sufficient to mediate trimerization. Our findings may have implications for vaccine development and therapeutic drug design strategies targeting spike trimerization. As global efforts for developing SARS-CoV-2 vaccines are rapidly underway, we believe this observation is an important consideration for identifying crucial epitopes of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019. It was first reported in Wuhan, China and has since become a global health concern. Keeping in view, the magnitude of the problem, scientists around the globe are working to develop effective therapeutic strategies. This review focuses on previous findings regarding SARS-CoV, which may prove helpful in future research on SARS-CoV-2. In addition, it also highlights recent developments in medicine and biotechnology toward developing effective drugs and vaccines against SARS-CoV-2. This review will analyze available data on this topic and will help researchers develop new thoughts using information already available as a step toward developing novel therapeutic strategies against SARS-CoV-2.

Disclaimer The EAC/NSHFMD Guidelines represent the views of the EAC and NSHFMD, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC and NSHFMD is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC/NSHFMD Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC/NSHFMD Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC/NSHFMD Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC/NSHFMD Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.Members of the Working Group confirmed the lack of financial support/ conflict of interest. In the event of a conflict of interest being reported, the member (s) of the Working Group was (were) excluded from the discussion of sections related to the area of conflict of interest.E.B. Wataman professor, Dr. of Sci. (Med.) (Moldova); E.K. Kurlyanskaya, Cand. of Sci. (Med.) (Belarus); A.M. Noruzbaeva professor (Kyrgyzstan); V.A. Azizov professor (Azerbaijan); Zelveyan P.A., Dr. of Sci. (Med.) (Armenia)

A single square centimetre of the human skin can contain up to one billion microorganisms. These diverse communities of bacteria, fungi, mites and viruses can provide protection against disease, but can also exacerbate skin lesions, promote disease and delay wound healing. This review addresses the current knowledge surrounding the healthy skin microbiome and examines how different alterations to the skin microbial communities can contribute to disease. Current methodologies are considered, changes in microbial diversity and colonisation by specific microorganisms are discussed in the context of atopic dermatitis, psoriasis, acne vulgaris and chronic wounds. The recent impact of modern Westernised lifestyles on the human skin microbiome is also examined, as well as the potential benefits and pitfalls of novel therapeutic strategies. Further analysis of the human skin microbiome, and its interactions with the host immune system and other commensal microorganisms, will undoubtedly elucidate molecular mechanisms for disease and reveal gateways for novel therapeutic treatment strategies.

Background: LMNA-related dilated cardiomyopathy (DCM) or cardiolaminopathy is an autosomal dominant trait with complete penetrance resulting in left ventricular enlargement and cardiac dysfunction. LMNA mutations in DCM have been shown to cause to ventricular arrythmias and conduction deficits. The interplay between the LMNA gene and other cell types have yet to be fully elucidated. Notably, cardiolaminopathy patients present with prominent cardiac fibrosis, but the mechanistic link between LMNA mutations and the development of fibrosis remains inconclusive. Additionally, LMNA is expressed in the endothelium, and patients with cardiolaminopathy exhibit distinct endothelial dysfunction. Hypothesis: We hypothesize that LMNA mutations prompt a cascade of pathological alterations on the endothelium, causing vascular dysfunction and fibrosis through endothelial to mesenchymal transition (EndoMT). Aims: Next generation sequencing platforms are critical to identifying these epigenetic and transcriptomic changes in the endothelium. Combining sequencing technology with our iPSC platform, we aim to unravel the mechanism behind vascular dysfunction and fibrosis in LMNA-DCM to uncover novel therapeutic targets and treatment strategies. Methods: We performed single nuclei multiome (RNA and ATAC) on cardiac tissue from one patient with LMNA-dilated cardiomyopathy. Frozen tissues were minced into pieces before digestion. We then utilized patient-specific induced pluripotent stem cells (iPSCs) and CRISPR-generated isogenic controls. We differentiated to endothelial cells (iPSC-ECs) and nuclei capture was performed after 24hr flow. Results: Endothelial cell clusters from cardiac tissue exhibit increased stress and mesenchymal markers. Phenotypic shift and EC dysfunction was corroborated with iPSC-ECs derived from two LMNA-DCM patients. Conclusion: These results present important considerations highlighting vascular dysfunction in LMNA-DCM and notes the importance of the endothelium in cardiac health. By analyzing these datasets produced from LMNA-DCM cardiac tissue and our iPSC-EC platform, there is opportunity to both define the mechanisms that causes cardiac fibrosis and to develop new therapeutic strategies.

Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in RHO. The high allelic heterogeneity of RHO mutations suggests complicated pathogenic mechanisms. Here, we discuss representative RHO mutations as examples to briefly summarize the mechanisms underlying rhodopsin-related retinal dystrophy, which include but are not limited to endoplasmic reticulum stress and calcium ion dysregulation resulting from protein misfolding, mistrafficking, and malfunction. Based on recent advances in our understanding of disease mechanisms, various treatment methods, including adaptation, whole-eye electrical stimulation, and small molecular compounds, have been developed. Additionally, innovative therapeutic treatment strategies, such as antisense oligonucleotide therapy, gene therapy, optogenetic therapy, and stem cell therapy, have achieved promising outcomes in preclinical disease models of rhodopsin mutations. Successful translation of these treatment strategies may effectively ameliorate, prevent or rescue vision loss related to rhodopsin mutations.