KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

In this focused review, we address the role of the kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen (PSA), in the regulation of angiogenesis. Early studies suggest that KLK3 is able to inhibit angiogenic processes, which is most likely dependent on its proteolytic activity. However, more recent evidence suggests that KLK3 may also have an opposite role, mediated by the ability of KLK3 to activate the (lymph)angiogenic vascular endothelial growth factors VEGF-C and VEGF-D, further discussed in the review.     

A Glimpse at the Size of the Fetal Liver—Is It Connected with the Evolution of Gestational Diabetes?

Gestational diabetes mellitus (GDM) is defined as an impairment of glucose tolerance, manifested by hyperglycemia, which occurs at any stage of pregnancy. GDM is more common in the third trimester of pregnancy and usually disappears after birth. It was hypothesized that the glycemic status of the mother can modulate liver development and growth early during the pregnancy. The simplest modality to monitor the evolution of GDM employs noninvasive techniques. In this category, routinely obstetrical ultrasound (OUS) examinations (simple or 2D/3D) can be employed for specific fetal measurements, such as fetal liver length (FLL) or volume (FLV). FLL and FLV may emerge as possible predictors of GDM as they positively relate to the maternal glycated hemoglobin (HbA1c) levels and to the results of the oral glucose tolerance test. The aim of this review is to offer insight into the relationship between GDM and fetal nutritional status. Risk factors for GDM and the short- and long-term outcomes of GDM pregnancies are also discussed, as well as the significance of different dietary patterns. Moreover, the review aims to fill one gap in the literature, investigating whether fetal liver growth can be used as a predictor of GDM evolution. To conclude, although studies pointed out a connection between fetal indices and GDM as useful tools in the early detection of GDM (before 23 weeks of gestation), additional research is needed to properly manage GDM and offspring health.     

Neurogenic Inflammation in the Context of Endometriosis—What Do We Know?

Endometriosis (EM) is an estrogen-dependent disease characterized by the presence of epithelial, stromal, and smooth muscle cells outside the uterine cavity. It is a chronic and debilitating condition affecting ~10% of women. EM is characterized by infertility and pain, such as dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Although EM was first described in 1860, its aetiology and pathogenesis remain uncertain. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with EM but also contribute to a growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. Here we review the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the role of this system, as well as its interactions with immune cells, will unearth novel disease-relevant pathways and targets, providing new therapeutics and better-tailored treatment options.     

Threat at One End of the Plant: What Travels to Inform the Other Parts?

Adaptation and response to environmental changes require dynamic and fast information distribution within the plant body. If one part of a plant is exposed to stress, attacked by other organisms or exposed to any other kind of threat, the information travels to neighboring organs and even neighboring plants and activates appropriate responses. The information flow is mediated by fast-traveling small metabolites, hormones, proteins/peptides, RNAs or volatiles. Electric and hydraulic waves also participate in signal propagation. The signaling molecules move from one cell to the neighboring cell, via the plasmodesmata, through the apoplast, within the vascular tissue or—as volatiles—through the air. A threat-specific response in a systemic tissue probably requires a combination of different traveling compounds. The propagating signals must travel over long distances and multiple barriers, and the signal intensity declines with increasing distance. This requires permanent amplification processes, feedback loops and cross-talks among the different traveling molecules and probably a short-term memory, to refresh the propagation process. Recent studies show that volatiles activate defense responses in systemic tissues but also play important roles in the maintenance of the propagation of traveling signals within the plant. The distal organs can respond immediately to the systemic signals or memorize the threat information and respond faster and stronger when they are exposed again to the same or even another threat. Transmission and storage of information is accompanied by loss of specificity about the threat that activated the process. I summarize our knowledge about the proposed long-distance traveling compounds and discuss their possible connections.     

What Are the Biomarkers for Immunotherapy in SCLC?

Small-cell lung cancer (SCLC) is an aggressive malignancy that exhibits a rapid doubling time, a high growth fraction, and the early development of widespread metastases. The addition of immune checkpoint inhibitors to first-line chemotherapy represents the first significant improvement of systemic therapy in several decades. However, in contrast to its effects on non-SCLC, the advantageous effects of immunotherapy addition are modest in SCLC. In particular, only a small number of SCLC patients benefit from immune checkpoint inhibitors. Additionally, biomarkers selection is lacking for SCLC, with clinical trials largely focusing on unselected populations. Here, we review the data concerning the major biomarkers for immunotherapy, namely, programmed death ligand 1 expression and tumour mutational burden. Furthermore, we explore other potential biomarkers, including the role of the immune microenvironment in SCLC, the role of genetic alterations, and the potential links between neurological paraneoplastic syndromes, serum anti-neuronal nuclear antibodies, and outcomes in SCLC patients treated with immunotherapy.     

Reassessment of the Identity of the Blue Light Emitter in Copper‐Containing Pyrotechnic Flames – Is it really CuCl?

While it is commonly thought that the molecular species responsible for the emission of blue light in fireworks flames is CuCl, a review of the physicochemical data obtained on gaseous CuCl vapors indicates that the actual emitter is the trimer Cu₃Cl₃. The literature is reviewed with regard to this issue, and a few experiments which might resolve the question are proposed.     

Removal of Monochloroacetic Acid in Water by Advanced Oxidation Based on Ozonation in the Presence of TiO2 Irradiated at λ > 340 nm

TiO₂ photocatalysis is based on the photoexcitation of electrons from the valence band to the conduction band. Increasing the rate of photocatalytic reactions requires decreasing the rate r at which the electrons are de-excited back to the valence band. Ozone was expected to be a good candidate to lower r on the basis that it is a much better electron scavenger than oxygen. In addition, it does not leave residues. To illustrate that, monochloroacetic acid (MCAA) was chosen as a model water pollutant since MCAA itself or its intermediate oxidation products do not directly react with O₃ and since it is nonvolatile. At a dose rate of 290 mg h^?1 of nonphotoexcited O₃, the MCAA removal rate at pH 3.4 and 7 was multiplied by a factor of ca. 7 in both distilled and tap water. TOC associated with MCAA was removed at about the same rate as MCAA. Cl^? ions were gradually oxidized into ClO₃ ^? ions. The chemistry underlying these O₃ effects is discussed.     

Glucose Metabolism in Burns—What Happens?

Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient’s health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel “ready to use” by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.     

Enrofloxacin—The Ruthless Killer of Eukaryotic Cells or the Last Hope in the Fight against Bacterial Infections?

Enrofloxacin is a compound that originates from a group of fluoroquinolones that is widely used in veterinary medicine as an antibacterial agent (this antibiotic is not approved for use as a drug in humans). It reveals strong antibiotic activity against both Gram-positive and Gram-negative bacteria, mainly due to the inhibition of bacterial gyrase and topoisomerase IV enzymatic actions. The high efficacy of this molecule has been demonstrated in the treatment of various animals on farms and other locations. However, the use of enrofloxacin causes severe adverse effects, including skeletal, reproductive, immune, and digestive disorders. In this review article, we present in detail and discuss the advantageous and disadvantageous properties of enrofloxacin, showing the benefits and risks of the use of this compound in veterinary medicine. Animal health and the environmental effects of this stable antibiotic (with half-life as long as 3–9 years in various natural environments) are analyzed, as are the interesting properties of this molecule that are expressed when present in complexes with metals. Recommendations for further research on enrofloxacin are also proposed.     

Therapeutic Treatments for Osteoporosis—Which Combination of Pills Is the Best among the Bad?

Osteoporosis is a chronical, systemic skeletal disorder characterized by an increase in bone resorption, which leads to reduced bone density. The reduction in bone mineral density and therefore low bone mass results in an increased risk of fractures. Osteoporosis is caused by an imbalance in the normally strictly regulated bone homeostasis. This imbalance is caused by overactive bone-resorbing osteoclasts, while bone-synthesizing osteoblasts do not compensate for this. In this review, the mechanism is presented, underlined by in vitro and animal models to investigate this imbalance as well as the current status of clinical trials. Furthermore, new therapeutic strategies for osteoporosis are presented, such as anabolic treatments and catabolic treatments and treatments using biomaterials and biomolecules. Another focus is on new combination therapies with multiple drugs which are currently considered more beneficial for the treatment of osteoporosis than monotherapies. Taken together, this review starts with an overview and ends with the newest approaches for osteoporosis therapies and a future perspective not presented so far.     

Lactate Transporters in the Context of Prostate Cancer Metabolism: What Do We Know?

Metabolic changes during malignant transformation have been noted for many years in tumours. Otto Warburg first reported that cancer cells preferentially rely on glycolysis for energy production, even in the presence of oxygen, leading to the production of high levels of lactate. The crucial role of lactate efflux and exchange within the tumour microenvironment drew attention to monocarboxylate transporters (MCTs). MCTs have been recognized as promising targets in cancer therapy, and their expression was described in a large variety of tumours; however, studies showing how these isoforms contribute to the acquisition of the malignant phenotype are scarce and still unclear regarding prostate cancer. In this review, we focus on the role for MCTs in cell metabolism, supporting the development and progression of prostate cancer, and discuss the exploitation of the metabolic nature of prostate cancer for therapeutic and diagnostic purposes.     

Sentury’s High- automation Tire Production Line Starting Operation at the End of the Year

The 5 million units/year high-automation semi-steel tire production line newly built by Qingdao Sentury Tire Co., Ltd. will be put into operation at the end of the year. The key equipment in the whole production line is high-automatic and introduced from abroad. And the number of employee will be less than 230 persons, which is half of the existing employees in the factory.     

Growth Factors,Reactive Oxygen Species,and Metformin—Promoters of the Wound Healing Process in Burns?

Burns can be caused by various factors and have an increased risk of infection that can seriously delay the wound healing process. Chronic wounds caused by burns represent a major health problem. Wound healing is a complex process, orchestrated by cytokines, growth factors, prostaglandins, free radicals, clotting factors, and nitric oxide. Growth factors released during this process are involved in cell growth, proliferation, migration, and differentiation. Reactive oxygen species are released in acute and chronic burn injuries and play key roles in healing and regeneration. The main aim of this review is to present the roles of growth factors, reactive oxygen species, and metformin in the healing process of burn injuries.     

Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.     

Etiology of IBD—Is It Still a Mystery?

Inflammatory bowel diseases (IBD), including colitis ulcerosa and Crohn’s disease, are chronic diseases of the gastrointestinal tract for which the cause has not been fully understood. However, it is known that the etiology is multifactorial. The multidirectional network of interactions of environmental, microbiological and genetic factors in predisposed persons lead to an excessive and insufficiently inhibited reaction of the immune system, leading to the development of chronic inflammation of the gastrointestinal walls, the consequence of which is the loss of the function that the intestine performs, inter alia, through the process of fibrosis. Detailed knowledge of the pathways leading to chronic inflammation makes it possible to pharmacologically modulate disorders and effectively treatthese diseases. In this review, we described the primary and adaptive immune system response in the gut and the known immune pathogenetic pathways leading to the development of IBD. We also described the process leading to intestinal tissue fibrosis, which is an irreversible consequence of untreated IBD.     

The Role of MicroRNAs in Myocarditis—What Can We Learn from Clinical Trials?

Myocarditis is an inflammatory disease of the heart with a viral infection as the most common cause. It affects most commonly young adults. Although endomyocardial biopsy and cardiac magnetic resonance are used in the diagnosis, neither of them demonstrates all the required qualities. There is a clear need for a non-invasive, generally available diagnostic tool that will still remain highly specific and sensitive. These requirements could be possibly met by microribonucleic acids (miRNAs), which are small, non-coding RNA molecules that regulate many fundamental cell functions. They can be isolated from cells, tissues, or body fluids. Recently, several clinical studies have shown the deregulation of different miRNAs in myocarditis. The phase of the disease has also been evidenced to influence miRNA levels. These changes have been observed both in adult and pediatric patients. Some studies have revealed a correlation between the change in particular miRNA concentration and the degree of cardiac damage and inflammation. All of this indicates miRNAs as potential novel biomarkers in the diagnosis of myocarditis, as well as a prognostic tool for this condition. This review aims to summarize the current knowledge about the role of miRNAs in myocarditis based on the results of clinical studies.     

The Treatment of Dyslipidemia—What's Left in the Pipeline?

Dyslipidemia is a pathological alteration of serum lipid levels. The most common forms are either elevations of triglycerides or low density lipoprotein cholesterol associated with a reduction of high density lipoprotein cholesterol. Most frequently both forms of lipid disorders are combined. Elevations of free fatty acid blood levels are commonly not subsumed under the term dyslipidemia. However, free fatty acids should also be considered, as they are frequently associated with dyslipidemia and represent a risk factor for cardiovascular diseases. Dyslipidemias are among the major etiologic factors for arterial occlusive diseases. Resulting in fatal implications such as stroke and coronary heart disease, dyslipidemias contribute to the most prevalent causes of death. Lowering of low density lipoprotein and raising of high density lipoprotein cholesterol levels have been shown in both epidemiologic and intervention studies to decrease mortality. Established treatments of dyslipidemias are statins and fibrates. However, recent research has established some new potential therapeutic targets which are currently investigated in clinical trials. New therapeutic approaches include subtype selective, dual, and pan-agonists of the peroxisome proliferator activated receptor, inhibitors of the cholesterol ester transfer protein, Acyl-CoA-cholesterol-acyltransferase, squalene synthase, microsomal triglycerid-transfer-protein, and cholesterol absorption. Clinical implications of new drugs under investigation are discussed in this review.