New Solution for Stem Cell Manufacturing: 3D Printing and Microfluidics!

 | Post date: 2022/06/28 | 
A 3D printed modular microfluidic system consisting of two micromixers, one spiral microfluidic separator, and one microfluidic concentrator has been presented which can detach and separate mesenchymal stem cells (MSCs) from microcarriers (MCs) in a short time while maintaining the cell’s viability and functionality.
Microfluidic devices have shown promising applications in the bioprocessing industry. However, the lack of modularity and high cost of testing and error limit their implementation in the industry. Advances in 3D printing technologies have facilitated the conversion of microfluidic devices from research output to applicable industrial systems. The system can be multiplexed and scaled up to process large volumes of the industry. 
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Transmission electron microscopy: multi analysis device!

 | Post date: 2022/06/20 | 
Transmission electron microscopy (TEM) with its various imaging modes and analytical abilities, is now an indispensable tool for chemical and structural characterization at the nanoscale of all types of materials. It is a microscopy technique in which a beam of energetic electrons is transmitted through a sample and the interaction of electrons with the sample forms an image. The image is then magnified and focused onto an imaging device, such as a fluorescent screen, a layer of photographic film, or a sensor like a charge-coupled device. At lower magnifications TEM image contrast is due to differential absorption of electrons by the material due to differences in its composition or thickness. 
X-ray emission consequent to the interaction of the primary electron beam with the sample, can also be detected by an energy-dispersive spectrometer (EDS) within the TEM. As the resulting X-ray energies are characteristic of the atomic structure of the element they originated from, the spectra generated can be used to identify the constituent elements.
It is also possible to measure the loss of energy from the inelastic scattering of electrons in specimen transmission (EELS). This information can be used to infer elemental composition, chemical bonding, valence and conduction band electronic properties.

A scanning transmission electron microscope (STEM) is a type of TEM. While in TEM parallel electron beams are focused perpendicular to the sample plane, in STEM the beam is focused at a large angle and is converged into a focal point. The transmitted signal is collected as a function of the beam location as it is rastered across the sample.
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dostarlimab: in patients with mismatch repair–deficient stage II or III rectal adenocarcinoma!

 | Post date: 2022/06/13 | 
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Transplantation of a human liver following 3 days of ex situ normothermic preservation

 | Post date: 2022/06/6 | 
Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. In a recent study which has been done by the multidisciplinary Zurich research team,  transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion has been reported. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.
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High Performance Liquid Chromatography (HPLC)

 | Post date: 2022/05/30 | 
High Performance Liquid Chromatography (HPLC) is a form of column chromatography that pumps a sample mixture or analyte in a solvent (known as the mobile phase) at high pressure through a column with chromatographic packing material (stationary phase). The sample is carried by a moving carrier gas stream of helium or nitrogen. HPLC has been used for the direct quantification of individual ecdysteroids in biological samples. This requires of course high sensitivity because of the low concentrations encountered and adequate sample clean up. 
Reversed-phase HPLC (RP-HPLC) is the most commonly used mode of HPLC and, as the name implies, this mode is just the reverse of normal phase HPLC (NP-HPLC), whereby the stationary phase is more nonpolar than the eluting solvent. Generally, RP-HPLC has a nonpolar stationary phase, e.g., C18 silica, and a moderately polar aqueous mobile phase. 
In RP-HPLC there is strong attraction between the polar solvent and polar molecules in the mixture being passed through the column, but there is not much attraction between the hydrocarbon chains attached to the silica (the stationary phase) and the polar molecules in the solution. Therefore, polar molecules in the mixture spend most of their time moving with the solvent. Nonpolar compounds in the mixture tend to form attractions with the hydrocarbon groups because of van der Waals dispersion forces. They are less soluble in the solvent because of the need to break hydrogen bonds as they squeeze in between the water or methanol molecules. They spend less time in solution in the solvent, and this slows them down on their way through the column, which means longer retention time. In RP-HPLC the polar molecules travel through the column more quickly.
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Non-steroidal anti-inflammatory drugs (NSAIDs): a different mode of action than what was known previously

 | Post date: 2022/05/24 | 
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) enzymes and are ubiquitously used for their anti-inflammatory properties. However, COX inhibition alone fails to explain numerous clinical outcomes of NSAID usage. Screening commonly used NSAIDs in primary human and murine myeloid cells demonstrated that NSAIDs could be differentiated by their ability to induce growth/differentiation factor 15 (GDF15), independent of COX specificity. Using genetic and pharmacologic approaches, NSAID-mediated GDF15 induction was dependent on the activation of nuclear factor erythroid 2-related factor 2 (NRF2) in myeloid cells. Sensing by Cysteine 151 of the NRF2 chaperone, Kelch-like ECH-associated protein 1 (KEAP1) was required for NSAID activation of NRF2 and subsequent anti-inflammatory effects both in vitro and in vivo. Myeloid-specific deletion of NRF2 abolished NSAID-mediated tissue protection in murine models of gout and endotoxemia. This highlights a noncanonical NRF2-dependent mechanism of action for the anti-inflammatory activity of a subset of commonly used NSAIDs.
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kienbock's disease: any definitive treatment?

 | Post date: 2022/05/16 | 
Kienbock's Disease, also known as avascular necrosis (AVN), is the avascular necrosis of the lunate which can lead to progressive wrist pain and abnormal carpal motion. Diagnosis can be made with wrist radiographs in advanced cases but may require MRI for detection of early disease.
There is no single cause of Kienbock’s disease. It can be caused by multiple factors such as:
Skeletal variations, Trauma, and other medical conditions: Kienbock’s disease can be found more commonly in people who have medical conditions that affect blood supply. It is also associated with diseases like lupus, sickle cell anemia and cerebral palsy.
Although there's no single cure for Kienböck's disease, medications, immobilizing the wrist and surgery have been used for the management of the disease. 
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Triple whammy: Anyone who is taking a diuretic and a renin-angiotensin system (RSA) inhibitor for high blood pressure should be cautious about also taking ibuprofen!

 | Post date: 2022/05/9 | 
Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as “triple whammy”. Diuretics and RAS inhibitors, such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. Researchers at the University of Waterloo used computer-simulated drug trials to model the interactions of the three drugs and the impact on the kidney. They found that in people with certain medical profiles, the combination can cause acute kidney injury, which in some cases can be permanent. They utilized sex-specific computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that low water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI. Triple treatment involving an ACE inhibitor, furosemide, and NSAID results in blood pressure levels similar to double treatment with ACEI and furosemide. Additionally, the male and female hypertensive models act similarly in most situations, except for the ACE inhibitor and NSAID double treatment.
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May: High Blood Pressure Education Month!

 | Post date: 2022/05/3 | 
High blood pressure (hypertension) is a common condition in which the long-term force of the blood against your artery walls is high enough that it may eventually cause health problems, such as heart disease. Blood pressure is determined both by the amount of blood your heart pumps and the amount of resistance to blood flow in your arteries. The more blood your heart pumps and the narrower your arteries, the higher your blood pressure. A blood pressure reading is given in millimeters of mercury (mm Hg). It has two numbers.
  • Top number (systolic pressure). The first, or upper, number measures the pressure in your arteries when your heart beats.
  • Bottom number (diastolic pressure). The second, or lower, number measures the pressure in your arteries between beats. 

Most people with high blood pressure have no signs or symptoms, even if blood pressure readings reach dangerously high levels. A few people with high blood pressure may have headaches, shortness of breath or nosebleeds, but these signs and symptoms aren't specific and usually don't occur until high blood pressure has reached a severe or life-threatening stage.
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April 25th, DNA day!

 | Post date: 2022/04/26 | 
Many people believe that American biologist James Watson and English physicist Francis Crick discovered DNA in the 1950s. In reality, this is not the case. Rather, DNA was first identified in the late 1860s by Swiss chemist Friedrich Miescher. Then, in the decades following Miescher's discovery, other scientists--notably, Phoebus Levene and Erwin Chargaff--carried out a series of research efforts that revealed additional details about the DNA molecule, including its primary chemical components and the ways in which they joined with one another. Without the scientific foundation provided by these pioneers, Watson and Crick may never have reached their groundbreaking conclusion of 1953: that the DNA molecule exists in the form of a three-dimensional double helix.
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Human distal airways contain a multipotent secretory cell that can regenerate alveoli!

 | Post date: 2022/04/18 | 
The researchers, who report their findings in Nature, analyzed human lung tissue to identify the new cells, which they call respiratory airway secretory cells (RASCs). The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. In this study, they show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. 
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Heart disease and mental health disorders are related!

 | Post date: 2022/04/12 | 
The term “heart disease” refers to several types of heart conditions. The most common type of heart disease in the United States is coronary artery disease (CAD), which affects the blood flow to the heart. Decreased blood flow can cause a heart attack. Sometimes heart disease may be “silent” and not diagnosed until a person experiences signs or symptoms of a heart attack, heart failure, or an arrhythmia. When these events happen, symptoms may include1
  • Heart attack: Chest pain or discomfort, upper back or neck pain, indigestion, heartburn, nausea or vomiting, extreme fatigue, upper body discomfort, dizziness, and shortness of breath.
  • Arrhythmia: Fluttering feelings in the chest (palpitations).
  • Heart failure: Shortness of breath, fatigue, or swelling of the feet, ankles, legs, abdomen, or neck veins.

High blood pressure, high blood cholesterol, and smoking are key risk factors for heart disease. About half of people in the United States (47%) have at least one of these three risk factors. Several other medical conditions and lifestyle choices can also put people at a higher risk for heart disease, including

  • Diabetes
  • Overweight and obesity
  • Unhealthy diet
  • Physical inactivity
  • Excessive alcohol use
  • Mental health disorders 

A large and growing body of research shows that mental health is associated with risk factors for heart disease before a diagnosis of a mental health disorder and during treatment. These effects can arise both directly, through biological pathways, and indirectly, through risky health behaviors.

People experiencing depression, anxiety, stress, and even PTSD over a long period of time may experience certain physiologic effects on the body, such as increased cardiac reactivity (e.g., increased heart rate and blood pressure), reduced blood flow to the heart, and heightened levels of cortisol. Over time, these physiologic effects can lead to calcium buildup in the arteries, metabolic disease, and heart disease.

Evidence shows that mental health disorders—such as depression, anxiety, and PTSD—can develop after cardiac events, including heart failure, stroke, and heart attack. These disorders can be brought on after an acute heart disease event from factors including pain, fear of death or disability, and financial problems associated with the event.

Some literature notes the impact of medicines used to treat mental health disorders on cardiometabolic disease risk. The use of some antipsychotic medications has been associated with obesity, insulin resistance, diabetes, heart attacks, atrial fibrillation, stroke, and death.

Mental health disorders such as anxiety and depression may increase the chance of adopting behaviors such as smoking, inactive lifestyle, or failure to take prescribed medications. This is because people experiencing a mental health disorder may have fewer healthy coping strategies for stressful situations, making it difficult for them to make healthy lifestyle choices to reduce their risk for heart disease.
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Obesity risk: The consequences of sleep deficiency!

 | Post date: 2022/03/29 | 
researchers at Mayo Clinic, show that lack of sufficient sleep led to a 9% increase in total abdominal fat area and an 11% increase in abdominal visceral fat, compared to control sleep. Visceral fat is deposited deep inside the abdomen around internal organs and is strongly linked to cardiac and metabolic diseases.
Twelve healthy, nonobese individuals (9 males, age range 19 to 39 years) completed a randomized, controlled, crossover, 21-day inpatient study comprising 4 days of acclimation, 14 days of experimental sleep restriction (4 hour sleep opportunity) or control sleep (9 hour sleep opportunity), and a 3-day recovery segment. Repeated measures of energy intake, energy expenditure, body weight, body composition, fat distribution and circulating biomarkers were acquired. The results of this study indicated that sleep restriction combined with ad libitum food promotes excess energy intake without varying energy expenditure. Weight gain and particularly central accumulation of fat indicate that sleep loss predisposes to abdominal visceral obesity.
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Cataract: one of the most common eye problems!

 | Post date: 2022/03/29 | 

A cataract is a clouding of the normally clear lens of the eye. For people who have cataracts, seeing through cloudy lenses is a bit like looking through a frosty or fogged-up window. Clouded vision caused by cataracts can make it more difficult to read, drive a car (especially at night) or see the expression on a friend's face. Most cataracts develop slowly and don't disturb the eyesight early on. But with time, cataracts will eventually interfere with vision.
At first, stronger lighting and eyeglasses can be helpful in dealing with cataracts. But if impaired vision interferes with the usual activities, cataract surgery might be needed. Fortunately, cataract surgery is generally a safe, effective procedure.

Most cataracts develop when aging or injury changes the tissue that makes up the eye's lens. Proteins and fibers in the lens begin to break down, causing vision to become hazy or cloudy. Some inherited genetic disorders that cause other health problems can increase the risk of cataracts. Cataracts can also be caused by other eye conditions, past eye surgery or medical conditions such as diabetes. Long-term use of steroid medications, too, can cause cataracts to develop.
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Stress and Cancer: Is there any relationship?

 | Post date: 2022/03/25 | 
The notion that stress and cancer are interlinked has dominated lay discourse for decades. More recent animal studies indicate that stress can substantially facilitate cancer progression through modulating most hallmarks of cancer, and molecular and systemic mechanisms mediating these effects have been elucidated. However, available clinical evidence for such deleterious effects is inconsistent, as epidemiological and stress-reducing clinical interventions have yielded mixed effects on cancer mortality. 
The best quality clinical studies have followed up many people for several years. They have found no evidence that those who are more stressed are more likely to get cancer. However, it should be noted that animal studies leverage their ability to synchronize stress exposure with specific phases of cancer growth and metastasis that are critically prone to stress. By contrast, epidemiological studies and most clinical trials assessing stress-reducing psychosocial interventions did not focus on stress-prone phases, some of which cannot be identified and addressed clinically.
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Celiac disease, celiac sprue or gluten-sensitive enteropathy: an immune reaction to eating gluten!

 | Post date: 2022/03/22 | 
Celiac disease, sometimes called celiac sprue or gluten-sensitive enteropathy, is an immune reaction to eating gluten, a protein found in wheat, barley and rye. Celiac disease is a serious autoimmune disease that occurs in genetically predisposed people where the ingestion of gluten leads to damage in the small intestine. It is estimated to affect 1 in 100 people worldwide.
When people with celiac disease eat gluten (a protein found in wheat, rye and barley), their body mounts an immune response that attacks the small intestine. These attacks lead to damage on the villi, small fingerlike projections that line the small intestine, that promote nutrient absorption. When the villi get damaged, nutrients cannot be absorbed properly into the body. Celiac disease is hereditary, meaning that it runs in families. People with a first-degree relative with celiac disease (parent, child, sibling) have a 1 in 10 risk of developing celiac disease.
Celiac disease can develop at any age after people start eating foods or medicines that contain gluten. Left untreated, celiac disease can lead to additional serious health problems.
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Cellular rejuvenation therapy safely reverses signs of aging!

 | Post date: 2022/03/14 | 
Anti-aging seems to be a buzzword with creams and supplements everywhere claiming they have found the secret to eternal youth. Of course, none of these
truly work or if they do their effects are minimal. This may soon change. Scientists at the Salk Institute, in collaboration with Genentech, a member of the Roche group, have made a major breakthrough and safely reversed the aging process in middle-aged and elderly mice. They achieved this by partially resetting their cells to more youthful states.
Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the life span of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. In this study, they performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging. Long-term partial reprogramming lead to rejuvenating effects in different tissues, such as the kidney and skin, and at the organismal level; duration of the treatment determined the extent of the beneficial effects. The rejuvenating effects were associated with a reversion of the epigenetic clock and metabolic and transcriptomic changes, including reduced expression of genes involved in the inflammation, senescence and stress response pathways. Overall, their observations indicate that partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes. We further conclude that longer-term partial reprogramming regimens are more effective in delaying aging phenotypes than short-term reprogramming.
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Lupus: Causes, Symptoms, therapeutic methods, and perspective!

 | Post date: 2022/03/10 | 

Lupus is an autoimmune disease that occurs when the immune system attacks its own tissues and organs. Inflammation caused by lupus can affect many different body systems including joints, skin, kidneys, blood cells, brain, heart and lungs. Lupus can be difficult to diagnose because its signs and symptoms often mimic those of other ailments. A facial rash that resembles the wings of a butterfly unfolding across both cheeks is known as the most distinctive sign of lupus which occurs in many but not all cases of lupus. Some people are born with a tendency toward developing lupus, which may be triggered by infections, certain drugs or even sunlight. While there's no cure for lupus, treatments can help control symptoms.
The medications most commonly used to control lupus include Nonsteroidal anti-inflammatory drugs (NSAIDs). Over-the-counter NSAIDs, such as naproxen sodium (Aleve) and ibuprofen (Advil, Motrin IB, others), may be used to treat pain, swelling and fever associated with lupus.
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PLG nanoparticles: prevention of skin and lung fibrosis in scleroderma!

 | Post date: 2022/03/8 | 
Systemic sclerosis (SSc) is a chronic multisystem orphan disease with a highly variable clinical course, significant mortality and a poorly understood complex pathogenesis. Researchers found a unique immune cell plays a key role in the chronic inflammation and scarring in the lungs and skin of people with scleroderma. Short-term treatment of mice with a novel nanoparticle composed of a carboxylated FDA-approved biodegradable polymer, poly(lactic-co-glycolic) acid (PLG), which modulates activation and trafficking of MARCO+ inflammatory monocytes, markedly attenuated bleomycin-induced skin and lung inflammation and fibrosis. Mechanistically, in isolated cells in culture PLG nanoparticles inhibited TGF-β-dependent fibrotic responses in vitro. Thus MARCO+ monocytes are potent effector cells of skin and lung fibrosis, and can be therapeutically targeted in SSc using PLG nanoparticles.
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Amyotrophic lateral sclerosis (ALS)

 | Post date: 2022/03/3 | 

Amyotrophic lateral sclerosis (a-my-o-TROE-fik LAT-ur-ul skluh-ROE-sis), or ALS, is a progressive nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control. ALS is often called Lou Gehrig's disease, after the baseball player who was diagnosed with it. Doctors usually don't know why ALS occurs. Some cases are inherited. ALS often begins with muscle twitching and weakness in a limb, or slurred speech. Eventually, ALS affects control of the muscles needed to move, speak, eat and breathe. There is no cure for this fatal disease.
Signs and symptoms of ALS vary greatly from person to person, depending on which neurons are affected. It generally begins with muscle weakness that spreads and gets worse over time. Signs and symptoms might include:

  • Difficulty walking or doing normal daily activities
  • Tripping and falling
  • Weakness in your legs, feet or ankles
  • Hand weakness or clumsiness
  • Slurred speech or trouble swallowing
  • Muscle cramps and twitching in your arms, shoulders and tongue
  • Inappropriate crying, laughing or yawning
  • Cognitive and behavioral changes

ALS often starts in the hands, feet or limbs, and then spreads to other parts of your body. As the disease advances and nerve cells are destroyed, your muscles get weaker. This eventually affects chewing, swallowing, speaking and breathing.

There's generally no pain in the early stages of ALS, and pain is uncommon in the later stages. ALS doesn't usually affect your bladder control or your senses.
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