The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden. Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available. Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1–6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor–negative polyarthritis (range of 24.6–29.9%). Methotrexate (61–84%) and etanercept (24%–61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7–42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4–30.1%) followed by gastrointestinal disorders (11.5–19.6%). The most frequent ESIs were infections (75.3–89%). This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA. The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ).

In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.

In the context of the high incidence of cancer worldwide, state-of-the-art photodynamic therapy (PDT) has entered as a usual protocol of attempting to eradicate cancer as a minimally invasive procedure, along with pharmacological resources and radiation therapy. The photosensitizer (PS) excited at certain wavelengths of the applied light source, in the presence of oxygen releases several free radicals and various oxidation products with high cytotoxic potential, which will lead to cell death in irradiated cancerous tissues. Current research focuses on the potential of natural products as a superior generation of photosensitizers, which through the latest nanotechnologies target tumors better, are less toxic to neighboring tissues, but at the same time, have improved light absorption for the more aggressive and widespread forms of cancer. Curcumin incorporated into nanotechnologies has a higher intracellular absorption, a higher targeting rate, increased toxicity to tumor cells, accelerates the activity of caspases and DNA cleavage, decreases the mitochondrial activity of cancer cells, decreases their viability and proliferation, decreases angiogenesis, and finally induces apoptosis. It reduces the size of the primary tumor, reverses multidrug resistance in chemotherapy and decreases resistance to radiation therapy in neoplasms. Current research has shown that the use of PDT and nanoformulations of curcumin has a modulating effect on ROS generation, so light or laser irradiation will lead to excessive ROS growth, while nanocurcumin will reduce the activation of ROS-producing enzymes or will determine the quick removal of ROS, seemingly opposite but synergistic phenomena by inducing neoplasm apoptosis, but at the same time, accelerating the repair of nearby tissue. The latest curcumin nanoformulations have a huge potential to optimize PDT, to overcome major side effects, resistance to chemotherapy, relapses and metastases. All the studies reviewed and presented revealed great potential for the applicability of nanoformulations of curcumin and PDT in cancer therapy.

Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepatitis and hepatocarcinoma, saving millions of lives.

Benefits of photobiomodulation (PBM) have been known for several decades. More recently, PBM applied in sports offers a special chance to support the modeling of the performance and recovery. Increasingly complex physical activities and fierce competition in the world of sports generate a state of psycho-emotional and physical stress that can induce chronic fatigue syndrome, failure in physical training, predisposition to muscle damage, physical and emotional exhaustion etc., for which PBM could be an excellent solution. To evaluate and identify all risk factors and the influence of PBM on health and performance in sport and for a better understanding of its effects, we did a search for “Photobiomodulation and Sports” on PubMed, to update the PBM science applied in sports, and we retained for analysis the articles published from 2014 to date. The term “PBM” is recent, and we did not include previous studies with “low level laser therapy” or “LLLT” before 2014. In the present research, PBM has been shown to have valuable protective and ergogenic effects in 25 human studies, being the key to success for high performance and recovery, facts supported also by 22 animal studies. PBM applied creatively and targeted depending on sport and size of the level of physical effort could perfectly modulate the mitochondrial activity and thus lead to remarkable improvements in performance. PBM with no conclusive results or without effects from this review (14 studies from a total of 39 on humans) was analyzed and we found the motivations of the authors from the perspective of multiple causes related to technological limitations, participants, the protocols for physical activity, the devices, techniques and PBM parameters. In the near future, dose–response experiments on physical activity should be designed and correlated with PBM dose–response studies, so that quantification of PBM parameters to allow the energy, metabolic, immune, and neuro-endocrine modulation, perfectly coupled with the level of training. There is an urgent need to continuously improve PBM devices, delivery methods, and protocols in new ingenious future sports trials. Latest innovations and nanotechnologies applied to perform intracellular signaling analysis, while examining extracellular targets, coupled with 3D and 4D sports motion analysis and other high-tech devices, can be a challenge to learn how to maximize PBM efficiency while achieving unprecedented sports performance and thus fulfilling the dream of millions of elite athletes.

Alzheimer’s disease (AD), as a neurodegenerative disorder, usually develops slowly but gradually worsens. It accounts for approximately 70% of dementia cases worldwide, and is recognized by WHO as a public health priority. Being a multifactorial disease, the origins of AD are not satisfactorily understood. Despite huge medical expenditures and attempts to discover new pharmaceuticals or nanomedicines in recent years, there is no cure for AD and not many successful treatments are available. The current review supports introspection on the latest scientific results from the specialized literature regarding the molecular and cellular mechanisms of brain photobiomodulation, as a complementary method with implications in AD. State-of-the-art pharmaceutical formulations, development of new nanoscale materials, bionanoformulations in current applications and perspectives in AD are highlighted. Another goal of this review was to discover and to speed transition to completely new paradigms for the multi-target management of AD, to facilitate brain remodeling through new therapeutic models and high-tech medical applications with light or lasers in the integrative nanomedicine of the future. In conclusion, new insights from this interdisciplinary approach, including the latest results from photobiomodulation (PBM) applied in human clinical trials, combined with the latest nanoscale drug delivery systems to easily overcome protective brain barriers, could open new avenues to rejuvenate our central nervous system, the most fascinating and complex organ. Picosecond transcranial laser stimulation could be successfully used to cross the blood-brain barrier together with the latest nanotechnologies, nanomedicines and drug delivery systems in AD therapy. Original, smart and targeted multifunctional solutions and new nanodrugs may soon be developed to treat AD.