Recovery of walking after paralysis by regenerating neurons to their natural target region!

 | Post date: 2023/09/26 | 
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: The Neurotransmitter of Happiness!

 | Post date: 2023/09/19 | 

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.

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Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccine!

 | Post date: 2023/09/12 | 
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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Lymphoma: An Overview of Hodgkin and Non-Hodgkin Lymphomas and Their Mechanisms

 | Post date: 2023/09/5 | 
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Vitiligo: Available therapeutic methods, Limitations and Challenges!

 | Post date: 2023/08/8 | 
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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Blood Brain Barrier and Strategies for Delivering Therapeutics!

 | Post date: 2023/08/1 | 
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 Architecture and Evolution of the Human Skeletal Form!

 | Post date: 2023/07/25 | 
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): mechanism of action!

 | Post date: 2023/07/18 | 
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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Not eating enough of six key foods in combination is associated with a higher risk of cardiovascular disease (CVD) in adults!

 | Post date: 2023/07/11 | 
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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nonalcoholic steatohepatitis (NASH): Etiologies, Epidemiology, and Symptoms!

 | Post date: 2023/07/4 | 
Nonalcoholic fatty liver disease is now recognized as the most common liver disease in the United States, with a prevalence of approximately 5% in the general population and up to 25% to 75% in patients with obesity and type II diabetes mellitus. Nonalcoholic fatty liver disease is a clinicopathologic syndrome with a wide spectrum of histologic abnormalities and clinical outcomes. Hepatic steatosis has a benign clinical course. In contrast, nonalcoholic steatohepatitis (NASH) may progress to cirrhosis and liver-related death in 25% and 10% of patients, respectively. Cases occur most commonly in obese, middle-aged women with diabetes. However, NASH may also occur in children and normal-weight men with normal glucose and lipid metabolism. The pathophysiology involves two steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Although antioxidant therapy with vitamin E is often used, ursodeoxycholic acid is the only drug that has shown benefit and is the most promising of the drugs currently being investigated. Future therapies will depend on a greater understanding of the pathophysiology and should focus on diminishing fibrosis.
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Acoustic-Powered Tiny Medical Microrobots May be Able to Treat Bladder Disease!

 | Post date: 2023/06/20 | 
Remotely powered microrobots are proposed as next-generation vehicles for drug delivery. However, most microrobots swim with linear trajectories and lack the capacity to robustly adhere to soft tissues. This limits their ability to navigate complex biological environments and sustainably release drugs at target sites. In this work, bubble-based microrobots with complex geometries are shown to efficiently swim with non-linear trajectories in a mouse bladder, robustly pin to the epithelium, and slowly release therapeutic drugs. The asymmetric fins on the exterior bodies of the microrobots induce a rapid rotational component to their swimming motions of up to ≈150 body lengths per second. Due to their fast speeds and sharp fins, the microrobots can mechanically pin themselves to the bladder epithelium and endure shear stresses commensurate with urination. Dexamethasone, a small molecule drug used for inflammatory diseases, is encapsulated within the polymeric bodies of the microrobots. The sustained release of the drug is shown to temper inflammation in a manner that surpasses the performance of free drug controls. This system provides a potential strategy to use microrobots to efficiently navigate large volumes, pin at soft tissue boundaries, and release drugs over several days for a range of diseases.
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A brain–spine interface: Walking naturally after spinal cord injury!

 | Post date: 2023/06/6 | 
A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis. In a recent study, the researchers restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain–spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking. A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis. A man paralyzed in 2011 has regained the ability to stand and walk with the help of implants placed in his brain and spinal cord. The patient, 40-year-old Gert-Jan Oskam of the Netherlands, was told he would never walk again after a biking accident. He suffered severe but partial damage to his spinal cord, which paralyzed his legs and partially paralyzed his arms.
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How exercise protects against brain strokes?

 | Post date: 2023/05/23 | 
In a recent study, published in the journal of Stroke and Vascular Neurology at Sahlgrenska University Hospital in Gothenburg, the researchers showed Regular physical activity and exercise may reduce bleeding in individuals with intracerebral hemorrhage. according to the results of this study which evaluated  686 people treated for intracerebral hemorrhage between 2014 and 2019, individuals who engaged in regular physical activity had, on average, bleeding volumes that were 50 percent smaller upon arriving to the hospital. 
Prestroke physical activity (PA) has been linked to improved outcomes after intracerebral haemorrhage (ICH), but its association with ICH volume is unknown. Intracerebral hemorrhage is the most dangerous type of stroke and can lead to life-threatening conditions. The risk of severe consequences from the hemorrhage increases with the extent of the bleeding.
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Mitochondrial replacement therapy (MRT) and three-person in vitro fertilization (IVF)!

 | Post date: 2023/05/16 | 

Mitochondrial replacement therapy (MRT), also known as mitochondrial donation, is a cutting-edge reproductive technology aimed at preventing the transmission of certain mitochondrial diseases from parent to child. Mitochondria are essential components of cells responsible for generating energy, and when they malfunction, it can lead to severe health issues.

MRT involves the transfer of healthy mitochondria from a donor to an individual or couple who carries mitochondrial DNA mutations or abnormalities. This technique offers hope to families affected by mitochondrial diseases, as it allows them to have healthy children while minimizing the risk of passing on these genetic conditions.

There are two primary techniques used in mitochondrial replacement therapy:

a. Pronuclear Transfer: This method involves transferring the nuclear DNA from the intended parents' embryo into a donor embryo that has had its nuclear DNA removed. The resulting embryo contains the intended parents' nuclear DNA and healthy mitochondria from the donor.

b. Maternal Spindle Transfer: In this technique, the nucleus is removed from the intended mother's egg before it is fertilized. The nucleus is then transferred into a donor egg that has had its nucleus removed. This reconstructed egg, with the intended mother's nuclear DNA and healthy mitochondria from the donor, is fertilized with sperm.
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Bridging the Gap: Artificial Intelligence in Revolutionizing Brain Hemorrhage Diagnosis

 | Post date: 2023/05/10 | 
Brain hemorrhage, also known as intracranial hemorrhage, is a potentially life-threatening problem that has many direct and indirect causes. Brain hemorrhages can result from various causes, including head trauma, high blood pressure, certain medications, blood vessel abnormalities, and bleeding disorders. Symptoms can vary depending on the location and severity of the hemorrhage but may include severe headache, nausea, vomiting, weakness, numbness, difficulty speaking or understanding speech, vision changes, seizures, and loss of consciousness.

There are different types of brain hemorrhages, including:

  1. Intracerebral hemorrhage: This occurs when blood vessels within the brain rupture and bleed into the surrounding tissue.

  2. Subarachnoid hemorrhage: This type of hemorrhage involves bleeding into the space between the brain and the tissues that cover it.

  3. Epidural hemorrhage: It occurs when bleeding occurs between the skull and the outermost covering of the brain (dura mater).

  4. Subdural hemorrhage: This involves bleeding between the dura mater and the brain's surface.

Accuracy in diagnosing the presence and type of intracranial hemorrhage is a critical part of effective treatment. Diagnosis is often an urgent procedure requiring review of medical images by highly trained specialists and sometimes necessitating confirmation through clinical history, vital signs, and laboratory examinations. The process is complicated and requires immediate identification for optimal treatment.​​​​​​ Artificial intelligence (AI) can play a valuable role in assisting with the diagnosis of brain hemorrhage, a potentially life-threatening condition. 

Here are a few ways AI can contribute to the diagnosis of brain hemorrhage:

  1. Medical imaging analysis: AI algorithms can be trained to analyze medical imaging scans, such as computed tomography (CT) or magnetic resonance imaging (MRI), to detect signs of brain hemorrhage. These algorithms can quickly and accurately identify abnormalities, such as bleeding, in the brain.

  2. Pattern recognition: AI models can be trained on large datasets of brain hemorrhage cases, enabling them to recognize patterns and features that may indicate the presence of a hemorrhage. By comparing new cases to this trained knowledge, AI systems can provide insights and flag potential cases for further review by medical professionals.

  3. Decision support: AI can assist healthcare professionals by providing decision support systems based on established clinical guidelines and protocols. By inputting patient data, such as symptoms, medical history, and laboratory results, AI algorithms can offer recommendations or probabilities regarding the likelihood of a brain hemorrhage, helping doctors make more informed decisions.

  4. Risk assessment: AI can help in predicting the risk of brain hemorrhage in certain patient populations. By analyzing vast amounts of patient data, including demographics, medical history, and lifestyle factors, AI models can identify risk factors and calculate individualized risk scores. This information can aid in early intervention and preventive measures.
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Electric Stimulation: Heals Wounds Three Times as Fast!

 | Post date: 2023/05/2 | 
Chronic wounds are a major health problem for diabetic patients and the elderly -- in extreme cases they can even lead to amputation. Using electric stimulation, researchers in a project at Chalmers University of Technology, Sweden, and the University of Freiburg, Germany, have developed a method that speeds up the healing process, making wounds heal three times faster. Upon cutaneous injury, the human body naturally forms an electric field (EF) that acts as a guidance cue for relevant cellular and tissue repair and reorganization. However, the direct current (DC) flow imparted by this EF can be impacted by a variety of diseases. This work delves into the impact of DC stimulation on both healthy and diabetic in vitro wound healing models of human keratinocytes, the most prevalent cell type of the skin. The culmination of non-metal electrode materials and prudent microfluidic design allowed us to create a compact bioelectronic platform to study the effects of different sustained (12 hours galvanostatic DC) EF configurations on wound closure dynamics. Specifically, They compared if electrotactically closing a wound's gap from one wound edge (i.e., uni-directional EF) is as effective as compared to alternatingly polarizing both the wound's edges (i.e., pseudo-converging EF) as both of these spatial stimulation strategies are fundamental to the eventual translational electrode design and strategy. They found that uni-directional electric guidance cues were superior in group keratinocyte healing dynamics by enhancing the wound closure rate nearly three-fold for both healthy and diabetic-like keratinocyte collectives, compared to their non-stimulated respective controls. The motility-inhibited and diabetic-like keratinocytes regained wound closure rates with uni-directional electrical stimulation (increase from 1.0 to 2.8% h−1) comparable to their healthy non-stimulated keratinocyte counterparts (3.5% h−1). Their results bring hope that electrical stimulation delivered in a controlled manner can be a viable pathway to accelerate wound repair, and also by providing a baseline for other researchers trying to find an optimal electrode blueprint for in vivo DC stimulation.

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Melanocyte stem cells' role in hair turning gray!

 | Post date: 2023/04/25 | 
the results of a study conducted by researchers from NYU Grossman School of Medicine revealed that hair color is controlled by whether nonfunctional but continually multiplying pools of melanocyte stem cells (McSCs) within hair follicles get the signal to become mature cells that make the protein pigments responsible for color. For unknown reasons, the McSCs system fails earlier than other adult stem cell populations, which leads to hair greying in most humans and mice. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli. In this study, researchers show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cells and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

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Osteogenesis Imperfecta: Etiology, Epidemiology, Diagnosis, and Controlling!

 | Post date: 2023/04/18 | 
Osteogenesis imperfecta (OI), known as brittle bone disease, is a genetic disorder that prevents the formation of strong bones. Mutation in genes that carry the instructions for making type I collagen leads to OI. Collagen is an important protein that gives structure and strength to bones, so a mutation in collagen-related genes (usually a mutation in the COL1A1 or COL1A2) causes bones to be fragile and prone to breaking. Type I collagen is also in other connective tissues such as tendons, ligaments, lungs, skin, and etc. In addition to the skeletal issues, OI can also affect other organs, such as teeth, eyes, and ears. some people with OI may also experience hearing loss, respiratory problems, and joint laxity. 
Oi is a rare genetic disorder, with an estimated incidence of 1 in 10,000 to 20,000 live birth worldwide. the prevalence of OI varies among different populations and is thought to be higher in certain regions, such as the Middle East and North Africa. Though anyone can be born with OI, people with a family history of the disease are at greater risk of inheriting the disease through an abnormal gene that is passed on from one or both parents. Oi affects males and females equally.
Diagnosis of OI is based on skeletal and extra-skeletal clinical findings. Radiological studies reveal osteoporosis and the presence of Wormian bones. Bone densitometry confirms the low bone mass.
there is no definite treatment for OI. However, he treatment of OI is directed toward the specific symptoms that are apparent in each individual. Treatment is aimed at preventing symptoms, maintaining individual mobility, and strengthening bone and muscle. Attention to nutrition and overall physical and psychological well-being is also very important.

Given the severe clinical manifestations of OI and the limitations of current treatments, a clear unmet medical need exists for treatment of OI. Transplantation of mesenchymal stem cells (MSC) presents a potential new mode of treatment, specifically starting treatment before birth or as early as possible after birth, to prevent irreversible damage

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A synaptic amplifier of hunger for regaining body weight in the hypothalamus: Possible target for drugs to combat the yo-yo effect!

 | Post date: 2023/04/11 | 
Researchers from the Max Planck Institute for Metabolism Research and Harvard Medical School have now shown a synaptic amplifier of hunger for regaining body weight in the hypothalamus. Restricting caloric intake effectively reduces body weight, but most dieters fail long-term adherence to caloric deficit and eventually regain lost weight. Hypothalamic circuits that control hunger drive critically determine body weight; yet, how weight loss sculpts these circuits to motivate food consumption until lost weight is regained remains unclear. In this study, researchers probe the contribution of synaptic plasticity in discrete excitatory afferents on hunger-promoting AgRP neurons. They reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight. Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists. Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight. 
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Artificial Intelligence in Medicine!

 | Post date: 2023/04/4 | 
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