Modern Medical Laboratory Journal

Ahead of World Cancer Day, the International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization (WHO), unveiled the most recent global cancer burden estimates. Additionally, WHO shared findings from a survey conducted in 115 countries, revealing that a significant number of nations do not adequately fund essential cancer and palliative care services as part of universal health coverage (UHC).

The IARC estimates, based on the best sources of data available in countries in 2022, highlight the growing burden of cancer, the disproportionate impact on underserved populations, and the urgent need to address cancer inequities worldwide.

In 2022, there were an estimated 20 million new cancer cases and 9.7 million deaths. The estimated number of people who were alive within 5 years following a cancer diagnosis was 53.5 million. About 1 in 5 people develop cancer in their lifetime, approximately 1 in 9 men and 1 in 12 women die from the disease.
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Clustered Regularly Interspaced Short Palindromic Repeats, commonly known as CRISPR, has emerged as a groundbreaking gene-editing technology, revolutionizing the field of molecular biology. Originally discovered as part of the bacterial immune system, CRISPR has been adapted for precise manipulation of DNA sequences in various organisms, offering unprecedented opportunities in medicine, agriculture, and biotechnology. CRISPR was initially identified in bacteria as a defense mechanism against viral infections. The system consists of short, partially palindromic repeated DNA sequences interspersed with unique spacer sequences derived from past viral invasions. In conjunction with Cas proteins, CRISPR provides bacteria with the ability to recognize and eliminate specific viral DNA, creating a memory of past infections. The key to CRISPR's success lies in its molecular scissors – the Cas9 protein. When guided by a synthetic RNA molecule that matches a target DNA sequence, Cas9 precisely cleaves the DNA at the desired location. This targeted DNA break triggers cellular repair mechanisms, allowing for the introduction of specific genetic modifications.CRISPR has sparked a revolution in medical research and treatment. Its potential for precise gene editing opens avenues for developing therapies for genetic disorders, cancer, and infectious diseases. The ability to modify genes associated with hereditary conditions holds promise for personalized medicine, offering tailored treatments based on an individual's genetic makeup.
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Cervical cancer develops in a woman's cervix (the entrance to the uterus from the vagina). Almost all cervical cancer cases (99%) are linked to infection with high risk human papillomavirus (HPV), an extremely common virus transmitted through sexual contact. Although most infections with HPV resolve spontaneously and cause no symptoms, persistent infection can cause cervical cancer in women.

Cervical cancer is the 6th most common cancer in women in the Eastern Mediterranean Region. In 2020, an estimated 89,800 women were diagnosed with cervical cancer in the Region and more than 47,500 women died from the disease.

January is Cervical Cancer Awareness Month. It is a perfect opportunity to raise awareness about cervical cancer and HPV vaccination. This year, we are focusing on ending cervical cancer within a few generations as the theme for Cervical Cancer Awareness Month.

When diagnosed, cervical cancer is one of the most successfully treatable forms of cancer, as long as it is detected early and managed effectively. Cancers diagnosed in late stages can also be controlled with appropriate treatment and palliative care. With a comprehensive approach to prevent, screen and treat, we can end cervical cancer as a public health problem within a few generations.

On this Cervical Cancer Awareness Month, the messages are clear.

Get informed. Find out the facts about cervical cancer and the human papilloma virus (HPV) that causes it. Help educate other women in your life too.

Get screened. Cervical cancer screening typically starts at age 30 and is repeated periodically.

Get vaccinated. The HPV vaccine is given in 2 doses that should begin when a girl is between 9 and 14 years old.

Cervical Cancer Awareness Month also comes at a time when the world continues to recover from the COVID-19 pandemic, where substantial disruptions to essential health services persist. So during this month and beyond, let us work together, to build back healthier communities by improving access to HPV vaccination, screening, treatment for cervical pre-cancer and management of cervical cancer by 2030 and end cervical cancer within a few generations.
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Smoking is a major cause of cardiovascular disease (CVD) and causes approximately one of every four deaths from CVD. According to World Health Organization data, smoking determines 10% of all CVDs. Tobacco smoking usage causes approximately 6 million death per year throughout the world, in the United States almost 500,000 deaths can be attributed to smoking and about 10% of these deaths are caused from second-hand smoke exposure. Epidemiologic studies have supported the assumption that cigarette smoking increases the incidence of myocardial infarction and fatal coronary artery diseases. Chemicals in cigarette smoke cause the cells that line blood vessels to become swollen and inflamed. This can narrow the blood vessels and can lead to many cardiovascular conditions.
Atherosclerosis, in which arteries narrow and become less flexible, occurs when fat, cholesterol, and other substances in the blood form plaque that builds up in the walls of arteries. The opening inside the arteries narrows as plaque builds up, and blood can no longer flow properly to various parts of the body. Smoking increases the formation of plaque in blood vessels.
Coronary Heart Disease occurs when arteries that carry blood to the heart muscle are narrowed by plaque or blocked by clots. Chemicals in cigarette smoke cause the blood to thicken and form clots inside veins and arteries. Blockage from a clot can lead to a heart attack and sudden death.
Stroke is a loss of brain function caused when blood flow within the brain is interrupted. Strokes can cause permanent brain damage and death. Smoking increases the risk for strokes. Deaths from strokes are more likely among smokers than among former smokers or people who have never smoked.
Peripheral Arterial Disease (PAD) and peripheral vascular disease occur when blood vessels become narrower and the flow of blood to arms, legs, hands and feet is reduced. Cells and tissue are deprived of needed oxygen when blood flow is reduced. In extreme cases, an infected limb must be removed. Smoking is the most common preventable cause of PAD.
Abdominal Aortic Aneurysm is a bulge or weakened area that occurs in the portion of the aorta that is in the abdomen. The aorta is the main artery that carries oxygen-rich blood throughout the body. Smoking is a known cause of early damage to the abdominal aorta, which can lead to an aneurysm. A ruptured abdominal aortic aneurysm is life-threatening; almost all deaths from abdominal aortic aneurysms are caused by smoking. Women smokers have a higher risk of dying from an aortic aneurysm than men who smoke. Autopsies have shown early narrowing of the abdominal aorta in young adults who smoked as adolescents.
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The human gut microbiome impacts human brain health in numerous ways:
(1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation.
(2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system.
(3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity.
(4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence.
(5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.
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Britain's medicines regulator has authorized the world's first gene therapy treatment for sickle cell disease, in a move that could offer relief to thousands of people with the disease. The new medicine, Casgevy, works by targeting the problematic gene in a patient's bone marrow stem cells so that the body can make properly functioning hemoglobin. Patients first receive a course of chemotherapy to make space for the new cells. Then, doctors take stem cells from the patient's bone marrow and use genetic editing techniques in a laboratory to fix the gene. The cells are then infused back into the patient for a permanent treatment.

In a clinical trial of Casgevy for sickle cell disease, 28 of the 29 patients experienced no episodes of major pain – which can lead to them being hospitalised – for at least a year afterward. When the treatment was used for those with beta thalassemia, 39 of the 42 trial participants did not need to have a red blood cell transfusion for at least 12 months after receiving Casgevy. 
Sickle cell disease is caused by mutations in the beta-globin gene, leading to the production of abnormal hemoglobin, the oxygen-carrying molecule in red blood cells. Normal red blood cells are shaped like donuts, but in sickle cell disease, the abnormal hemoglobin causes red blood cells to stiffen and adopt a spiky, sickle-like shape. The disease is estimated to affect 100,000 people in the United States and is more common among Black Americans. Sickle cell disease can be cured with a donor bone marrow transplant but use of this therapy has the best chance of success in patients who have a closely matched sibling donor, which is only a minority of patients.
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Gene transcription, a pivotal process in molecular biology, is a highly regulated and intricate mechanism that enables the expression of genetic information. It commences as RNA polymerase recognizes and binds to a specific promoter region on DNA, initiating the unwinding of the DNA double helix. Subsequently, the enzyme synthesizes a complementary RNA strand using ribonucleotides along the template DNA strand. This process elongates the RNA molecule, which may undergo post-transcriptional modifications to become mature RNA, including mRNA, rRNA, and tRNA. The termination of transcription is signaled by specific sequences, leading to the release of the RNA transcript. The regulation of gene transcription plays a fundamental role in determining gene expression and, consequently, cellular functions and responses to various stimuli. This dynamic process allows for the precise control of protein production and the adaptation of cells to their environment.
The regulated transcription of genes determines cell identity and function. Recent structural studies have elucidated mechanisms that govern the regulation of transcription by RNA polymerases during the initiation and elongation phases. Microscopy studies have revealed that transcription involves the condensation of factors in the cell nucleus. A model is emerging for the transcription of protein-coding genes in which distinct transient condensates form at gene promoters and in gene bodies to concentrate the factors required for transcription initiation and elongation, respectively. The transcribing enzyme RNA polymerase II may shuttle between these condensates in a phosphorylation-dependent manner. Molecular principles are being defined that rationalize transcriptional organization and regulation, and that will guide future investigations.
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The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. In a recent study, the researchers estimated the abundance of the primary immune cell types throughout all tissues in the human body. They conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. They also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Their results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10¹² cells (95% CI 1.5–2.3 × 10¹²), weighing 1.2 kg (95% CI 0.8–1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tissues, account for 10% of immune cells but contribute nearly 50% of the total cellular mass due to their large size. The quantification of immune cells within the human body presented here can serve to understand the immune function better and facilitate quantitative modeling of this vital system.
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Researchers in Sweden have developed a 3D-printed, microscale implant in the eye to offer cell-based therapy that could treat diabetes. The researchers chose pancreatic islets, cell clusters in the pancreas that produce insulin, as donors’ cells have been used in experimental treatments for type 1 diabetes. 

Anna Herland, senior lecturer in the Division of Bionanotechnology at SciLifeLab at KTH and the AIMES research center at KTH and Karolinska Institutet, says that the eye is ideal for this technology because it has no immune cells that react unfavorably in the first stage of implantation. Its transparency allows visual and microscopic study of what happens to the implant over time.

“The eye is our only window into the body, and it’s immune-privileged,” Herland says.
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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, poses a significant global health challenge. This malignancy typically arises in the hepatocytes of the liver and is often associated with chronic liver disease. Several risk factors contribute to the development of HCC, including chronic hepatitis B and C infections, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and cirrhosis, which result from various etiologies. The key to managing HCC lies in early detection and intervention. While treatments vary based on the stage and severity of the disease, options include surgical resection, liver transplantation, radiofrequency ablation, transarterial chemoembolization, and systemic therapies like sorafenib and immunotherapies. As research into the molecular mechanisms of HCC advances, targeted therapies are emerging, offering new hope for more effective treatment options. The comprehensive approach to HCC, combining prevention, risk factor management, early diagnosis, and a range of therapeutic modalities, is crucial in addressing this formidable cancer and improving patient outcomes.
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A research team, led by Professor Ja Hyoung Ryu from the Department of Chemistry at UNIST, in collaboration with Professor Hyewon Chung from Konkuk University, has achieved a significant breakthrough in the treatment of age-related diseases. Their cutting-edge technology offers a promising new approach by selectively removing aging cells, without harming normal healthy cells. This groundbreaking development is poised to redefine the future of healthcare and usher in a new era of targeted therapeutic interventions. In their study, the team designed organic molecules that selectively target receptors overexpressed in the membranes of aging cells. By leveraging the higher levels of reactive oxygen species (ROS) found in aging cells, these molecules promote the formation of disulfide bonds and create oligomers that bind together.
Senolytics, which eliminate senescent cells from tissues, represent an emerging therapeutic strategy for various age-related diseases. Most senolytics target antiapoptotic proteins, which are overexpressed in senescent cells, limiting specificity and inducing severe side effects. To overcome these limitations, they constructed self-assembling senolytics targeting senescent cells with an intracellular oligomerization system. Intracellular aryl-dithiol-containing peptide oligomerization occurred only inside the mitochondria of senescent cells due to selective localization of the peptides by RGD-mediated cellular uptake into integrin α_vβ₃-overexpressed senescent cells and elevated levels of reactive oxygen species, which can be used as a chemical fuel for disulfide formation. This oligomerization results in an artificial protein-like nanoassembly with a stable α-helix secondary structure, which can disrupt the mitochondrial membrane via multivalent interactions because the mitochondrial membrane of senescent cells has weaker integrity than that of normal cells. These three specificities (integrin α_vβ₃, high ROS, and weak mitochondrial membrane integrity) of senescent cells work in combination; therefore, this intramitochondrial oligomerization system can selectively induce apoptosis of senescent cells without side effects on normal cells. Significant reductions in key senescence markers and amelioration of retinal degeneration were observed after elimination of the senescent retinal pigment epithelium by this peptide senolytic in an age-related macular degeneration mouse model and in aged mice, and this effect was accompanied by improved visual function. This system provides a strategy for the treatment of age-related diseases using supramolecular senolytics.
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Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, a team of researchers from UCLA applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. They show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.
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Dopamine is a fascinating neurotransmitter that plays a crucial role in our daily lives, influencing various aspects of our well-being, including happiness. Often referred to as the "feel-good" neurotransmitter, dopamine is involved in a wide range of functions within the brain and body. Let's explore how dopamine affects happiness, its underlying mechanisms, and how various substances and activities can influence its production.

Dopamine and Happiness:

Dopamine is often associated with feelings of pleasure, reward, and motivation. It's released in response to pleasurable experiences and serves as a biological signal that reinforces positive behaviors. This connection between dopamine and happiness is not only fascinating but also essential for understanding how we experience joy and satisfaction.

Mechanism of Dopamine in Happiness:

1. Reward Pathway: The brain's reward system, often called the mesolimbic pathway, is where dopamine shines. When you engage in activities that bring pleasure or reward, such as eating a delicious meal, winning an award, or receiving praise, your brain releases dopamine. This surge in dopamine reinforces the behavior, making you more likely to repeat it in the future.

2. Motivation and Goal Achievement: Dopamine also plays a crucial role in motivation. It encourages you to pursue and achieve goals, whether they are small tasks like completing a to-do list or larger life aspirations. The anticipation of the reward associated with accomplishing these goals triggers dopamine release, providing a sense of satisfaction and motivation to keep going.

Dopamine and Substances/Activities:

1. Coffee: Many people turn to coffee for a morning dopamine boost. Caffeine, a key component in coffee, can increase dopamine production. It stimulates the release of dopamine by blocking adenosine, another neurotransmitter that promotes relaxation. This temporary surge in dopamine can lead to improved mood and alertness.

2. Awards and Recognition: Receiving awards or recognition for your accomplishments can be a powerful source of dopamine. The acknowledgment of your efforts activates the brain's reward system, releasing dopamine and generating feelings of happiness and pride.

3. Exercise: Physical activity is another way to boost dopamine levels. Regular exercise has been shown to increase dopamine receptors in the brain, making it more sensitive to this neurotransmitter. This is why many people report feeling happier and more energized after a good workout.

4. Drugs of Abuse: Unfortunately, the same dopamine system that promotes happiness and motivation can be hijacked by drugs of abuse, such as cocaine and opioids. These substances artificially increase dopamine levels, leading to intense feelings of euphoria. However, repeated drug use can disrupt the brain's natural dopamine balance, leading to addiction and negative consequences.

In conclusion, dopamine is a key player in our pursuit of happiness. It's the brain's way of rewarding us for positive behaviors and motivating us to achieve our goals. While substances like coffee can provide a temporary dopamine boost, the most sustainable and healthy way to maintain a happy, balanced brain is through activities like exercise and the pursuit of meaningful accomplishments, like winning awards or achieving personal goals. Understanding the role of dopamine in our lives can help us make informed choices about how we seek and experience happiness.
https://journals.sagepub.com/doi/abs/10.1177/2631454118806139

To elicit optimal immune responses, messenger RNA vaccines require intracellular delivery of the mRNA and the careful use of adjuvants. MIT researchers report a multiply adjuvanted mRNA vaccine consisting of lipid nanoparticles encapsulating an mRNA-encoded antigen, optimized for efficient mRNA delivery and for the enhanced activation of innate and adaptive responses. They optimized the vaccine by screening a library of 480 biodegradable ionizable lipids with headgroups adjuvanted with cyclic amines and by adjuvanting the mRNA-encoded antigen by fusing it with a natural adjuvant derived from the C3 complement protein. In mice, intramuscular or intranasal administration of nanoparticles with the lead ionizable lipid and with mRNA encoding for the fusion protein (either the spike protein or the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) increased the titres of antibodies against SARS-CoV-2 tenfold with respect to the vaccine encoding for the unadjuvanted antigen. Multiply adjuvanted mRNA vaccines may improve the efficacy, safety and ease of administration of mRNA-based immunization.
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Vitiligo is a skin condition where patches of skin lose their color due to the loss of pigment-producing cells called melanocytes. The exact cause is complex and involves autoimmune, genetic, and environmental factors. The immune system attacks and destroys melanocytes, resulting in depigmented patches. Cellular and molecular processes include immune system dysfunction, oxidative stress, and genetic susceptibility. Further research is ongoing to fully understand these processes and develop effective treatments. The treatment of vitiligo, which aims at repigmentation, depends both on the clinical characteristics of the disease as well as on molecular markers that may predict the response to treatment. Therapies that combine more than one cell type, such as melanocytes and keratinocytes, or more than one method of treatment, such as the addition of NV-UVB to another treatment, increase the chances of >90% repigmentation. Neural crest cell-derived melanocytes are the melanin-producing cells of the skin; several melanocyte cell death mechanisms have been proposed to explain the origin of vitiligo. As such, the transplantation of healthy cells shows great promise for treating vitiligo patients. Several methods for the delivery of non-cultured melanocytes into the affected skin areas of patients have been attempted, including transplantation onto dermabraded or laser-abraded areas. In this approach, the skin sample is shortly incubated with trypsin and centrifuged before spreading on the recipient area. As the number of melanocytes in this method is not increased in culture, its efficacy might be lower compared to cultured melanocyte transplantation.
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The blood-brain barrier (BBB) is a highly specialized protective barrier that separates the blood circulation from the brain and spinal cord tissues. Its main function is to regulate the entry of substances into the brain, allowing essential nutrients and substances while restricting the passage of potentially harmful substances.

The BBB is composed of endothelial cells lining the blood vessels in the brain, held together by tight junctions that create a selective barrier. This barrier is further supported by astrocytes, a type of brain cell that surrounds the blood vessels and helps maintain the integrity of the BBB.

The mechanism of action of the blood-brain barrier involves several key features:
1. Tight Junctions: These are complex protein structures that seal the gaps between endothelial cells, forming a continuous barrier that restricts the movement of most molecules.
2. Specialized Transporters: Certain nutrients, like glucose and amino acids, are actively transported across the BBB through specific carrier proteins.
3. Efflux Pumps: The BBB employs efflux pumps to actively pump out potentially harmful substances or toxins that manage to penetrate the barrier.
4. Lipid Solubility: Lipid-soluble substances can diffuse through the lipid bilayer of endothelial cells, allowing them to cross the BBB more easily.

Overall, the blood-brain barrier plays a crucial role in protecting the brain from harmful substances while maintaining an environment essential for proper brain function. However, it also presents a challenge in delivering drugs to the brain for treating neurological disorders, as it can limit the passage of therapeutic agents. Researchers are exploring various strategies to develop drug delivery systems that can bypass or exploit the BBB to improve treatment options for brain-related conditions.

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The genetic changes that made possible the transition from knuckle-based scampering in great apes to upright walking in humans have now been uncovered in a new study by researchers at Columbia University and the University of Texas.
Using a combination of deep learning (a form of artificial intelligence) and genome-wide association studies, the researchers have created the first map of the genomic regions responsible for skeletal changes in primates that led to upright walking. The map reveals that genes that underlie the anatomical transitions observed in the fossil record were strongly acted on by natural selection and gave early humans an evolutionary advantage.
Many skeletal changes occurred on the path to modern humans, resulting in bipedalism but also susceptibility to musculoskeletal diseases. Kun et al. used imaging data from more than 30,000 UK Biobank participants to characterize skeletal proportions, assessing the genetic basis of these features, as well as their relationships to each other. They found that limb proportions are uncorrelated with body width proportions, that there are associations between hip- and leg-related skeletal proportions and osteoarthritis, and that there is enrichment for loci associated with skeletal proportion in genomic regions associated with human-specific evolution. The mentioned study demonstrated the utility of using imaging data from biobanks to understand both disease-related and normal physical variation among humans. 
Humans are the only bipedal great apes, owing to our distinctive skeletal form. Morphological changes that contribute to our skeletal form have been studied extensively in paleoanthropology. With the exception of standing height, examining the genetic basis for differential and specific growth of individual bones and their evolution has been challenging because of limited sample sizes.
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Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and joint destruction. The underlying mechanisms of RA involve a complex interplay between genetic factors, environmental triggers, and dysregulated immune responses. This abstract provides an overview of the key mechanisms involved in the pathogenesis of rheumatoid arthritis. The development of RA is influenced by genetic predisposition, with certain human leukocyte antigen (HLA) alleles, such as HLA-DRB1, being strongly associated with the disease. Environmental factors, such as smoking and certain infections, also contribute to disease susceptibility. In RA, the synovial tissue lining the joints becomes inflamed, leading to a cascade of events. Initially, activated immune cells, particularly T-cells, infiltrate the synovium and release pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These cytokines promote the recruitment and activation of other immune cells, including macrophages and B-cells.

Macrophages play a crucial role in RA pathogenesis. They contribute to persistent inflammation by producing additional pro-inflammatory cytokines and enzymes, such as matrix metalloproteinases (MMPs), which degrade joint tissues. Moreover, macrophages activate fibroblast-like synoviocytes, leading to synovial hyperplasia and pannus formation, a destructive tissue mass that invades and damages the joints. B-cells also participate in the pathogenesis of RA by producing autoantibodies, specifically rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPAs). These autoantibodies form immune complexes that further perpetuate the inflammatory response and contribute to joint damage. The dysregulated immune response in RA is also characterized by a disruption in the balance of regulatory T-cells and effector T-cells. This imbalance results in a loss of self-tolerance and the perpetuation of the autoimmune response.
The progressive joint destruction in RA involves the erosion of cartilage and bone. Activated synovial fibroblasts and osteoclasts contribute to this process, driven by the pro-inflammatory cytokines and growth factors present in the inflamed joint microenvironment. Understanding the intricate mechanisms involved in rheumatoid arthritis is essential for the development of targeted therapies that can modulate the immune response, alleviate inflammation, and prevent joint damage. Advancements in this field have led to the emergence of biological agents, such as TNF inhibitors, interleukin inhibitors, and B-cell targeted therapies, which have revolutionized the treatment landscape for RA patients and improved their quality of life.

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A study led by McMaster University and Hamilton Health Sciences researchers at the Population Research Health Institute (PHRI) has found that not eating enough of six key foods in combination is associated with a higher risk of cardiovascular disease (CVD) in adults. A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0–6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63–0.77)], CVD (HR 0.82; 0.75–0.91), myocardial infarction (HR 0.86; 0.75–0.99), and stroke (HR 0.81; 0.71–0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66–0.81), CVD (HR 0.79; 0.72–0.87), myocardial infarction (HR 0.85; 0.71–0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73–1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65–0.80] and stroke (OR 0.57; 0.50–0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison).
A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

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