Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?

Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.     

Why Rhodium in Automotive Three-Way Catalysts?

The catalytic treatment of motor vehicle exhaust gas has been a feature of all passenger cars in the USA since the 1975 model year. It has since been adopted in all the developed countries as the principal means of con-trolling the emissions from vehicles powered by Otto-cycle internal com-bustion engines. These include passenger cars, light trucks, and heavy-duty trucks. Catalysts have been developed for motorcycles and even smaller power plants. The so-called three-way catalyst (TWC) has been in use since the 1979 model year. The name reflects the simultaneous treatment by this catalyst of the two reducing pollutants, carbon monoxide and uncombusted hydrocarbons, and the oxidizing pollutant, oxides of nitrogen.     

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.     

Why Are We Creating Less Garbage?

Something odd happened to our garbage a couple decades ago. We started creating less of it. According to a new study by researchers at the Earth Engineering Center at City College of New York, sometime around the late 1990s we began to see a decrease in the rate at which we generate waste compared to economic growth. Typically, as gross domestic product (GDP) increases, the amount of trash increases along with it, at about the same rate. The authors note that both GDP and waste generation tracked each other from 1960 on, as expected—until the late 1990s. Then, as GDP continued to climb, waste generation began to climb more slowly. We were getting richer, but we were creating less waste     

AMP-Activated Protein Kinase: Do We Need Activators or Inhibitors to Treat or Prevent Cancer?

AMP-activated protein kinase (AMPK) is a key regulator of cellular energy balance. In response to metabolic stress, it acts to redress energy imbalance through promotion of ATP-generating catabolic processes and inhibition of ATP-consuming processes, including cell growth and proliferation. While findings that AMPK was a downstream effector of the tumour suppressor LKB1 indicated that it might act to repress tumourigenesis, more recent evidence suggests that AMPK can either suppress or promote cancer, depending on the context. Prior to tumourigenesis AMPK may indeed restrain aberrant growth, but once a cancer has arisen, AMPK may instead support survival of the cancer cells by adjusting their rate of growth to match their energy supply, as well as promoting genome stability. The two isoforms of the AMPK catalytic subunit may have distinct functions in human cancers, with the AMPK-α1 gene often being amplified, while the AMPK-α2 gene is more often mutated. The prevalence of metabolic disorders, such as obesity and Type 2 diabetes, has led to the development of a wide range of AMPK-activating drugs. While these might be useful as preventative therapeutics in individuals predisposed to cancer, it seems more likely that AMPK inhibitors, whose development has lagged behind that of activators, would be efficacious for the treatment of pre-existing cancers.     

Why Does Industry Not Use Immobilized Transition Metal Complexes as Catalysts?

Much effort has gone into the immobilization of homogeneous catalysts based on the idea that in this way the catalysts could be not only separated more easily from the product but also reused several times, thus reducing the cost of the catalyst use. So far none of these immobilized catalysts have been used by industry. In this article we critically review the use of immobilized homogeneous catalysts from the point of view of process development for the pharmaceutical and fine chemical industry. The first and foremost question that needs to be answered is: will immobilizing a homogeneous catalyst really lead to lower costs? The answer is thus far always no. This is caused mostly by the fact that homogeneous catalysts are not stable and thus there is little point in immobilizing them. The second reason is the extra added cost that is incurred in immobilizing the catalysts. Other problems are lower rates, sometimes lower selectivities and metal leaching. Three different areas are discussed. The research on immobilized metathesis catalysts is analyzed in detail; in general the immobilized catalysts do not achieve sufficient turnovers to be interesting for industrial use. Very many publications have appeared on immobilized palladium catalysts that were used for C C bond‐forming reactions, such as Suzuki, Heck or Sonogashira reactions. These catalysts are invariably converted to nanoparticles after the first run. Although these catalysts can be reused, there is no reason to use an expensive support based on immobilized ligands. This also does not protect the product from palladium contamination. Even more effort has gone into the immobilization of homogeneous hydrogenation catalysts. Most of these catalysts suffer from the same problems as the other immobilized catalysts: catalyst deactivation, low turnover numbers, and leaching of the metal. In addition, the heterogenization adds complexity to the system, increasing risk and prolonging process development.

     

How Far is the Concept of Isolated Active Sites Valid in Solid Catalysts?

Oxide catalysts that have open structures and contain cations exhibiting usually just one or a few oxidation states, and those that are close-packed and contain transition metal ions in many different oxidation states are contrasted from the viewpoint of the concept of site isolation in heterogeneous catalysts. Much valuable progress can be made in this way to design new solid catalysts that are viable for the production of a wide range of compounds such as bulk or commodity chemicals (adipic acid and caprolactam), builder molecules (epoxides and lactones), as well as some fine chemicals and vitamins. The close-packed, multiple-valence oxide structures are also of enormous importance in the context of commercial manufacture of such vital commodities as acrolein, acrylic acid and acrylonitrile. It is thought that new techniques are still needed (to supplement the powerful insights gained from electron microscopy and other approaches) to unravel the mechanistic details involved in the operation of the Mars–van Krevelen (MVK) way of effecting catalytic selective oxidations. It has recently transpired that the MVK mechanism operates when certain metal catalysts (e.g. Pt, Pd) effect selective oxidations at pressures and temperatures under which they are used commercially.     

Can a Single Atom Serve as the Active Site in Some Heterogeneous Catalysts?

We examine a number of distinct situations relating to heterogeneous catalysts where either a single atom (or ion), or a very small cluster of atoms functions as the locus of chemical turnover in various distinct kinds of conversion. There is little doubt that individual ions at certain crystallographic sites in nanoporous solids can indeed act as single-site catalysts. The situation concerning nanoclusters of pure metal (or bimetallic entities) is rather more ambiguous. What was hitherto thought to be an effective catalyst made up of a small cluster of Pt supported on ??-Al₂O₃ (for hydrogenation) now seems to be a single atom of Pt attached to a 5-coordinated Al^III ion. And in the case of Au or Pt on other supports, there is evidence that a single Pt atom, positively charged, but surrounded by alkali-metal ions, is a powerful catalyst for the water?Cgas shift (CO + H₂O ?? H₂ + CO₂) reaction. We also report interesting results concerning the mobility of CeO₂ support material.     

What Kind of Rubber Machinery Equipm ent Do Tire Enterprises Need?

<正>Improving quality, enhancing efficiency and lowering the cost is an eternal demand of tire enterprises for rubber machinery equipment. On National Tire Industry Equipment and Technology Application Seminar held in Jiangyin on May 10, Sun Huaijian,an expert in tire industry, expressed that as long as the rubber machinery enterprises could research and develop relevant equipment according to the demand of the tire industry, the tire factories surely would purchase them.     

Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?

Endometrial cancer is one of the most common malignant diseases in women worldwide, with an incidence of 5.9%. Thus, it is the most frequent cancer of the female genital tract, with more than 34,000 women dying, in Europe and North America alone. Endometrial Cancer Stem Cells (CSC) might be drivers of carcinogenesis as well as metastatic and recurrent disease. Therefore, targeting CSCs is of high interest to improve prognosis of patients suffering of advanced or recurrent endometrial cancer. This review describes the current evidence of molecular mechanisms in endometrial CSCs with special emphasis on MYC and NF-κB signaling as well as mitochondrial metabolism. Furthermore, the current status of immunotherapy targeting PD-1 and PD-L1 in endometrial cancer cells and CSCs is elucidated. The outlined findings encourage novel therapies that target signaling pathways in endometrial CSCs as well as immunotherapy as a promising therapeutic approach in the treatment of endometrial cancer to impede cancer progression and prevent recurrence.     

Circadian Rhythms in Legumes: What Do We Know and What Else Should We Explore?

The natural timing devices of organisms, commonly known as biological clocks, are composed of specific complex folding molecules that interact to regulate the circadian rhythms. Circadian rhythms, the changes or processes that follow a 24-h light–dark cycle, while endogenously programmed, are also influenced by environmental factors, especially in sessile organisms such as plants, which can impact ecosystems and crop productivity. Current knowledge of plant clocks emanates primarily from research on Arabidopsis, which identified the main components of the circadian gene regulation network. Nonetheless, there remain critical knowledge gaps related to the molecular components of circadian rhythms in important crop groups, including the nitrogen-fixing legumes. Additionally, little is known about the synergies and trade-offs between environmental factors and circadian rhythm regulation, especially how these interactions fine-tune the physiological adaptations of the current and future crops in a rapidly changing world. This review highlights what is known so far about the circadian rhythms in legumes, which include major as well as potential future pulse crops that are packed with nutrients, particularly protein. Based on existing literature, this review also identifies the knowledge gaps that should be addressed to build a sustainable food future with the reputed “poor man’s meat”.     

Normalization of the Immunological Microenvironment and Sustained Minimal Residual Disease Negativity: Do We Need Both for Long-Term Control of Multiple Myeloma?

Over the past two decades, the treatment landscape for multiple myeloma (MM) has progressed significantly, with the introduction of several new drug classes that have greatly improved patient outcomes. At present, it is well known how the bone marrow (BM) microenvironment (ME) exerts an immunosuppressive action leading to an exhaustion of the immune system cells and promoting the proliferation and sustenance of tumor plasma cells. Therefore, having drugs that can reconstitute a healthy BM ME can improve results in MM patients. Recent findings clearly demonstrated that achieving minimal residual disease (MRD) negativity and sustaining MRD negativity over time play a pivotal prognostic role. However, despite the achievement of MRD negativity, patients may still relapse. The understanding of immunologic changes in the BM ME during treatment, complemented by a deeper knowledge of plasma cell genomics and biology, will be critical to develop future therapies to sustain MRD negativity over time and possibly achieve an operational cure. In this review, we focus on the components of the BM ME and their role in MM, on the prognostic significance of MRD negativity and, finally, on the relative contribution of tumor plasma cell biology and BM ME to long-term disease control.     

Nanoparticles for Targeted Brain Drug Delivery: What Do We Know?

The blood–brain barrier (BBB) is a barrier that separates the blood from the brain tissue and possesses unique characteristics that make the delivery of drugs to the brain a great challenge. To achieve this purpose, it is necessary to design strategies to allow BBB passage, in order to reach the brain and target the desired anatomic region. The use of nanomedicine has great potential to overcome this problem, since one can modify nanoparticles with strategic molecules that can interact with the BBB and induce uptake through the brain endothelial cells and consequently reach the brain tissue. This review addresses the potential of nanomedicines to treat neurological diseases by using nanoparticles specially developed to cross the BBB.     

Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death. Although the burden of alcohol- and NASH-related HCC is growing, chronic viral hepatitis (HBV and HCV) remains a major cause of HCC development worldwide. The pathophysiology of viral-related HCC includes liver inflammation, oxidative stress, and deregulation of cell signaling pathways. HBV is particularly oncogenic because, contrary to HCV, integrates in the cell DNA and persists despite virological suppression by nucleotide analogues. Surveillance by six-month ultrasound is recommended in patients with cirrhosis and in “high-risk” patients with chronic HBV infection. Antiviral therapy reduces the risks of development and recurrence of HCC; however, patients with advanced chronic liver disease remain at risk of HCC despite virological suppression/cure and should therefore continue surveillance. Multiple scores have been developed in patients with chronic hepatitis B to predict the risk of HCC development and may be used to stratify individual patient’s risk. In patients with HCV-related liver disease who achieve sustained virological response by direct acting antivirals, there is a strong need for markers/scores to predict long-term risk of HCC. In this review, we discuss the most recent advances regarding viral-related HCC.     

Atherosclerosis in HIV Patients: What Do We Know so Far?

For the past several decades, humanity has been dealing with HIV. This disease is one of the biggest global health problems. Fortunately, modern antiretroviral therapy allows patients to manage the disease, improving their quality of life and their life expectancy. In addition, the use of these drugs makes it possible to reduce the risk of transmission of the virus to almost zero. Atherosclerosis is another serious pathology that leads to severe health problems, including disability and, often, the death of the patient. An effective treatment for atherosclerosis has not yet been developed. Both types of immune response, innate and adaptive, are important components of the pathogenesis of this disease. In this regard, the peculiarities of the development of atherosclerosis in HIV carriers are of particular scientific interest. In this review, we have tried to summarize the data on atherosclerosis and its development in HIV carriers. We also looked at the classic therapeutic methods and their features concerning the concomitant diagnosis.