MicroRNA for treating cancer and asthma

A microRNA that regulates inflammation shows promise as a treatment for inflammatory diseases such as asthma and cancer. The microRNA, known as miR-223, is highly expressed in blood cells that cause inflammation (neutrophils). When they're working correctly, those blood cells protect the body against infections, but sometimes they damage host tissue instead of microbes, causing chronic inflammation and disease.

To uncover the link between miR-223 and inflammation, a Purdue University research team created a zebrafish totally deficient of miR-223. Then they cut off a small chunk of its fin. "The inflammation was really robust," said Qing Deng, a professor of biological sciences at Purdue and corresponding author of the paper. "Neutrophils accumulated at the wound and they just kept coming. This is consistent with the literature, but we wanted to understand why."

Extensive gene expression analysis led them to pathway NF-kB, a protein complex found in nearly all animal cell types that regulates inflammation and cell proliferation. Heightened activation of this pathway is the cause of increased inflammation, although it's limited to the deeper, or basal, layer of the epithelium. This means any therapeutics would need to reach the basal layer to work.

The same pathway plays an important role in human bronchial epithelial cells, which are critical in the development of asthma, according to the study. MiR-223 suppresses the pathway, which means supplementing it to epithelial cells could help control inflammatory disease.
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Immune signature predicts asthma susceptibility

Asthma is a chronic inflammatory disease driven by the interplay of genetics, environmental factors and a diverse cast of immune cells. Researchers at La Jolla Institute for Allergy and Immunology (LJI) identified a subset of T cells, whose frequency serves as early childhood immune signature that predicts the risk of developing asthma later on.

Children who, at the age of one, had a higher frequency of MAIT cells appear to be less likely to develop asthma by the age of seven. Consistent with the "hygiene hypothesis," which holds that increased microbial exposure in the first years of life is protective for asthma, the team's findings also indicate that the presence of house dust components that stimulate the innate immune system decreases asthma risk.

Unlike conventional T cells, which belong to the adaptive arm of the immune response and take a few days before they are fully trained on a single, specific protein fragment or peptide antigen, MAIT and iNKT cells recognize molecular components common to many microbes. The team analyzed the frequency of different types of immune cells in blood collected from 110 one year-old study participants, the presence of immune-stimulatory components in the subjects' house dust and asked whether any of the factors correlated with an increased of asthma at age seven.

Certain immune signatures such as having more MAITs that are protective in humans MAIT cells are unique in that they are borne to make gamma interferon, which could help skew the immune system toward an asthma-protective. And while the absolute numbers of iNKT cells had no bearing on asthma risk, the iNKT cell antigenic content in house dust from subjects' houses did. iNKT activity reflects a home environment with increased microbe exposure and prevents asthma.
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Bacteria in milk linked to rheumatoid arthritis

A strain of bacteria found in milk and beef may be a trigger for developing rheumatoid arthritis in people who are at risk, according to a new study from the University of Central Florida. A team of UCF College of Medicine researchers has discovered a link between rheumatoid arthritis and Mycobacterium avium subspecies paratuberculosis, known as MAP, a bacteria found in about half the cows in the United States. The bacteria can be spread to humans through the consumption of infected milk, beef and produce fertilized by cow manure.

For the study, researchers recruited 100 of her patients who volunteered clinical samples for testing. Seventy-eight percent of the patients with rheumatoid arthritis were found to have a mutation in the PTPN2/22 gene, the same genetic mutation found in Crohn's patients, and 40 percent of that number tested positive for MAP. People born with this genetic mutation and who are later exposed to MAP through consuming contaminated milk or meat from infected cattle are at a higher risk of developing rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune and inflammatory disease that causes the immune system to attack a person's joints, muscles, bones and organs. Patients suffer from pain and deformities mostly in the hands and feet. It can occur at any age but the most common onset is between 40 and 60 years old and is three times more prevalent in women. Some RA patients suffer from Crohn's disease and vice versa, the researchers say a national study needs to investigate the incidence of the two diseases in the same patients.
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Vitamin D may prevents Rheumatoid arthritis

Maintaining sufficient vitamin D levels may prevent the onset of inflammatory diseases like rheumatoid arthritis, it is less effective once inflammatory disease is established because diseases such as rheumatoid arthritis leads to vitamin D insensitivity. The impact of vitamin D on inflammatory disease cannot be predicted using cells from healthy individuals or even from the blood of patients with inflammation as cells from the disease tissue are different.

If vitamin D is to be used in patients with rheumatoid arthritis, clinicians may need to prescribe much higher doses than currently provide a treatment that also corrects the vitamin D insensitivity of immune cells within the joint. Vitamin D is a potent modulator of the immune system. In particular, vitamin D can suppress inflammation in autoimmune diseases such as rheumatoid arthritis. Patients with rheumatoid arthritis are frequently vitamin D deficient and may receive vitamin D supplementation.

The study involved using paired peripheral blood and synovial fluid from the inflamed joint of patients with rheumatoid arthritis. The current understanding of vitamin D and rheumatoid arthritis is based on studies of patient blood which may not truly represent the situation at the site of inflammation -the joints. Investigating responses to the active form of vitamin D in immune cells from the inflamed joints of patients with rheumatoid arthritis compared to blood from the same patients, the inflamed joint immune cells were much less sensitive to active vitamin D.

This occurred because immune cells from the joints of rheumatoid arthritis patients are more committed to inflammation, and therefore less likely to change, even when they respond to vitamin D. Maintaining sufficient vitamin D may prevent the onset of inflammatory diseases like rheumatoid arthritis. However, for patients who already have rheumatoid arthritis, providing vitamin D might not be enough. Instead much higher doses of vitamin D may be needed, or possibly a new treatment that corrects the vitamin D insensitivity of immune cells within the joint.
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Immune and nerve cells fight gut infections

Nerve cells in the gut play a crucial role in the body's ability to produce an immune response to infection. The immune system and nervous system worked together to respond to infectious threats.

The immune system and neuronal system don't act independently,
The lining of the gut house many immune system cells, which serve as a defense against parasites and other infections.

It is also loaded with nerve cells, immune system cells in the gut, called group 2 innate lymphoid cells (ILC2s), are intertwined with nerve cells called cholinergic neurons.

The ILC2 cells have a receptor for a protein called neuromedin U (NMU), which acts as a messenger for the nerve cells. Exposing ILC2 cells to NMU causes the ILC2 cells to multiply rapidly and secrete chemicals called cytokines that may help trigger an immune response or cause inflammation.

Administering NMU to mice infected with a gut parasite triggered inflammation and a powerful
immune response that expel the parasites quickly.

This shows that the NMU-producing nerve cells help the ILC2 cells, enabling them to rapidly and effectively respond to infection. The findings may improve fighting and provision of therapies for inflammatory diseases like asthma, food allergies and inflammatory bowel diseases.
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Cyltezo for chronic inflammatory diseases

Cyltezo is for the treatment of multiple chronic inflammatory diseases, including: moderate to severe active rheumatoid arthritis, moderate to severe polyarticular juvenile idiopathic arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderate to severe active adult Crohn’s disease,
moderate to severe active ulcerative colitis and moderate to severe plaque psoriasis

Patients treated with adalimumab products, including Cyltezo, are at increased risk for developing serious infections that may lead to hospitalization or death.

Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease.

Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.

Do not start Cyltezo during an active infection, including localized infections.
Patients older than 65 years, patients with co-morbid conditions and patients taking concomitant immunosuppressants may be at greater risk of infection.

Cyltezo for patients with these disorders; discontinuation of Cyltezo should be considered if any of these disorders develop.
Hematological Reactions
Congestive Heart Failure
Autoimmunity
Patients on Cyltezo should not receive live vaccines.
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Antibiotics drug resistance gonorrhoea

Gonorrhoea is sexually-transmitted infection that is difficult to treat. It can be transmitted through vaginal, anal and oral intercourse.

The bacterium that causes gonorrhea can be contacted by touching an infected area or person. The bacteria that cause gonorrhoea resist different antibiotics.

 Gonorrhoea can infect the genitals, rectum and throat. Common complications of gonorrhoea are abdominal pain, pelvic inflammatory disease, ectopic pregnancy and risk of HIV and infertility.

Pregnant women can infect their babies through child birth and it will leads to blindness. The United Nations health agency advises doctors to prescribe two antibiotics- ceftriaxone and azithromycin for gonorrhoea. It can be prevented by consistent and correct use of condom.
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