Cause of fatal disease that turns babies' lips, skin blue identified

Scientists using gen-editing tool. CRISPR/ Cas9 have identified the cause -- and a potential treatment -- of a fatal respiratory disorder newborn infants that turns their lips and skin blue.

The team used CRISPR/Cas9 to generate mice that mimic the mostly untreatable disorder called Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). 

The model allowed researchers in the US to pinpoint the ailment's cause and develop a potential and desperately needed nano-particle-based treatment.

ACDMPV usually strikes infants within a month of birth. The disease starves the pulmonary system of oxygen after the lung's blood vessels do not form properly during organ development.

The lack of tiny blood vessels called alveolar capillaries causes hypoxia, inflammation and death, researchers said.

"There are no effective treatments other than a lung transplant, so the need for new therapeutics is urgent," said a Dr.

"We identified a nano-particle therapeutic strategy to increase the number of alveolar capillaries and help preserve respiratory function for at least a subset of the babies with this congenital lung disease," said the lead researcher in the study.

The disease has long been linked to mutations in the FOXF1 gene, an important regulator of embryonic lung development.

The remaining mystery until this study is precise microbiological processes that fuel ACDMPV, researchers said.

Researchers analysed genetic information from human ACDMPV cases to generate the first clinically relevant animal model of ACDMPV. They used CRISPR/ Cas9 to recreate human FOXF1 mutations in the mouse.

CRISPR-Cas9 allows precise gene editing by using an enzyme to cut out specific sections of a DNA sequence and reattaching the loose ends at a desired point to change a cell's genetic makeup.

Having clinically accurate mouse models of disease ACDMPV allowed the scientists to overcome a longtime hurdle to understanding how the disease develops, researchers said.

By studying protein-DNA interactions linked to the FOXF1 gene in pulmonary cells, researchers found a specific point mutation, which blocked molecular signalling to multiple downstream target genes involved in formation of pulmonary blood vessels.

The researchers theorised that treating newborn mice with a protein called STAT3 would stimulate blood vessel development in the lungs.

Researchers turned to nano-particle technology to deliver a STAT3 mini-gene to lungs of newborn mice. They created a novel formulation for what are known as polyethylenimine (PEI) nanoparticles.

The gelatin-like PEI nanoparticles can carry therapeutic genetic material to different parts of the body by administering them to patients intravenously.

Different formulations of PEI nanoparticles are currently being tested in clinical trials for adult cancer at other institutions, researchers said.

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DIFFERENCE BETWEEN NTURAL RIPENING AND ARTIFICIAL RIPENING OF FRUITS

Food safety and health security should be top concerns of any Government for its citizens. But still, most of the fruit sellers use Chemicals like Calcium carbide for ripening the fruits. This Chemical is extremely hazardous to the human body as it contains traces of arsenic and phosphorus. Although it is banned in many countries of the world, it is freely used in Indian Subcontinent. Thus, we are at a greater risk of short-term as well as long-term health effects simply by eating fruits that are artificially ripened.
Artificial ripening of fruits is done to achieve faster and more uniform ripening characteristics at the cost of its Nutritional Values.

 So, what is the basic difference between the Natural and Artificial ripening of the Fruits?
Natural ripening is a physiological process which makes the fruit edible, palatable and nutritious. In nature, fruits ripen after attainment of proper maturity by a sequence of complex physical and biochemical events. Whether fruits ripen on the plant or after harvest, the general ripening changes associated with the process are easily recognisable. During ripening fruits soften, changes colour, and characteristic aroma and flavours develop. During the process of ripening several factors like temperature, humidity etc. acts as a catalyst. Whereas in the case of artificial ripening, fruit ripening agents promote ripening and induce colour changes. Although the appearance of such artificially ripened fruits has been found to be improved, the taste and smell are found to be impaired especially when harvested fruits were subjected to treatment without considering their maturity status. Besides, the quantity required of the ripening agent to induce ripening will be much more than the conventional dose, when the fruits are not mature enough.

What are Fruit ripening agents?

 Ripening agents speed up the process of ripening of fruits after they are picked prior to full ripening. These agents are particularly Unsaturated hydrocarbons; acetylene, ethylene, etc. However, a chemical known as Calcium Carbide (CaC2) is most commonly used for artificial ripening of fruits. Calcium carbide, when hydrolysed, produces acetylene, which causes artificial ripening of fruits. Other than the Calcium Carbide following Chemicals are in common practice in artificially ripening of the fruits:

Ethylene: A very small concentration of ethylene in air is sufficient to promote the fruit ripening process. Externally applied Ethylene is likely to trigger or initiate the natural ripening process of apple, avocado, banana, mango, papaya, pineapple and guava, and therefore, can be sold before the predicted time.

Ethephon: Ethephon is another agent which is used to artificially ripen fruits. Ethephon is often considered better in terms of taking less time than calcium carbide for ripening. The fruits ripened with Ethephon have more acceptable colour than naturally ripened fruits and have longer shelf life than fruits ripened with Calcium carbide.

Ripening of fruits with Ethylene and Ethephon is permissible if used in a limited concentration. Many countries including India has allowed the use of Ethylene and Ethephon for ripening of fruits as it is less harmful if compared with Calcium carbide. But many petitions have been filed to ban these chemicals too due to the indiscriminate use by the traders and the farmers as they lack the knowledge of their proper use.

Effects of Calcium Carbide on fruit quality

Mostly the Fruits which are grown on orchards are sent to distant markets which sometimes takes several days to reach in ordinary or refrigerated transportation. Usually, these fruits go through the Ripening process in those markets before retailing. And for that, all that a trader has to do is to wrap a small quantity of Calcium Carbide in a packet of paper and keep this packet near a pile or box of fruits. Because of moisture content in the fruit, a chemical reaction takes place which releases heat and acetylene gas are produced, which rushes the ripening process. After which they are kept in ice for lowering the temperature and to develop the colour. However, fruits ripened with Calcium carbide are often soft and less tasty, and they also have a shorter storage life.

Ban on using Calcium Carbide

Considering its hazardous effects, Calcium Carbide is banned in many countries including India, but despite the ban, it is widely used in the Indian Subcontinent. The concerned authorities have failed to carve out any effective action plan to check the malpractices in ripening. In India, artificial ripening is banned under the Prevention of Food Adulteration (PFA) Act, 1954, and the Prevention of Food Adulteration Rules, 1955. According to rules 44AA of the PFA Rules 1955, no fruit can be ripened with the aid of Calcium Carbide. Those convicted under this Act could face imprisonment for three years and a fine of up to Rupees 1000. Several news reports have highlighted the open indiscriminate use of Calcium Carbide in different parts of the country. But there are hardly any cases where the traders or retailers involved in Artificial ripening have been booked.

How to identify Artificially Ripened fruits?

All that glitters is not gold and is definitely harmful these days. Fruits that look attractive outside may not be good for health. Fruits that have a uniform colour are more likely to have been artificially ripened. The naturally ripened fruits are not uniformly coloured; rather, they are patchy. When tomatoes are uniformly red, or mango and papaya are uniformly orange/yellow, then Calcium Carbide may have been used. Bananas can also be identified if the fruits are all yellow green whereas the stem is dark. While purchasing fruits and vegetables, remember not to select those that are homogenously ripened and with bright, eye-catching colours. The habit of washing and peeling before eating the fruit could help in minimising the health risks associated with the use of Calcium Carbide. It is better to cut the fruit into pieces, rather than to consume them directly. And it is not advisable to buy fruits when they arrive in the market before the due period i.e. early and off-season.

What are the Health hazards associated with these Chemicals?

Calcium carbide is a known carcinogen, a cancer-producing chemical. Irrespective of what quantity you may consume, the chemical is known to have harmful effects on the liver and other parts of the body. It also contains traces of arsenic and phosphorus hydride. Which produces several acute and chronic health effects. The early symptoms of arsenic or phosphorus poisoning include vomiting, burning sensation in the chest and abdomen, diarrhoea, thirst, weakness, difficulty in swallowing, irritation or burning of the eyes and skin, permanent eye damage, ulcers on the skin, irritation in the mouth, nose and throat. Throat sores, cough, and wheezing and shortness of breath may also occur soon after exposure to the chemical. Higher exposure may cause a build-up of fluids in the lungs. Eating artificially ripened mangoes causes stomach upset because the alkaline substance is an irritant that erodes the mucosal tissue in the stomach and disrupts intestinal function. Prolonged exposure to the chemical could lead to peptic ulcer.

In humans, acetylene is not acutely toxic if it is below the permissible levels whereas if it exceeds the limits then its inhalation can cause unconsciousness and it may affect the neurological system by inducing prolonged hypoxia i.e. deficiency of Oxygen. Findings related to carbide poisoning have reported headache, dizziness, memory loss, mood disturbances, mental confusion, sleepiness, cerebral oedema and seizure. Other effects include numbness in the legs and hands, general weakness, cold and damp skin and low blood pressure. Although most cases of arsenic and phosphorus poisoning are detected before they become fatal, pregnant women are particularly vulnerable as the chemical residue in the fruit could lead to miscarriage.

How to Stop this Practice?

For fruit traders, the point of using chemicals is to speed up the ripening process so that they can cash-in immediately. But if the Government does not approve of using Artificial ripening for fruits, how can these fruit traders use them? It is obvious that the practice of using calcium carbide is an unnatural practice, and when the Government is disapproving, the fruit traders cannot proceed with this unhealthy practice. The fruit traders are saying that they are using its small quantity, but who is going to keep control of how much they are using? It is not possible for the authorities to go and check every fruit seller. But following measures can help in keeping a check on this practice:

• On procurement and selling of these banned Chemicals, restrictions should be strictly imposed.
• The fruit traders and sellers should be made aware of the health hazards and imbued with a sense of moral responsibility to the society.
• Vigilance at the wholesale markets should be strengthened to stop the practice.
• Environmentally safe new compounds which are not harmful to human health must be discovered and tested.

Artificial Fruit ripening is a complex issue especially in developing countries like India and requires the combined involvement of the whole community, government agencies, policymakers, fruit-sellers, farmers, scientists and consumers to find an effective solution to this matter. 

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Tumour hardness may develop cancer cells

Tumour hardness and hypoxia -- lack of oxygen at the tumour's core -- trigger a biological switch that causes cancer stem cells to develop, a recent study has found. This biological switch is critical to a tumour's ability to invade other tissue -- a process called metastasis. 

 "Our study suggests that to combat cancer, we should be developing treatments that target the stiff, hypoxic regions of tumours. We were surprised to see just how important these two properties in the tumour micro-environment -- stiffness and hypoxia -- were for regulating cancer stem cells," said Celeste Nelson, Professor at the Princeton University, in the US. The cancer stem cells that specialise in generating new malignant cells represent only a small proportion of the total cells in a tumour, but researchers believe they play a key role in spreading the disease.

Using cultures of human breast-cancer cells and mouse mammary-cancer cells, Nelson and her colleagues discovered an association between a protein called integrin-linked kinase and the creation of cancer stem cells. The researchers created a range of human and mouse breast-cancer cultures reflecting different tissue conditions and showed that stiff hypoxic cultures did indeed promote cancer stem cells. But when they eliminated the integrin-linked kinase from those samples, they found that the cancer stem cells stopped forming. Conversely, when they forced abnormal levels of integrin-linked kinase in samples containing softer or less hypoxic tissue, cancer stem cells formed. They also confirmed a significant association between tumour stiffness, integrin-linked kinase and cancer stem cell presence in samples from human breast-cancer patients. 

 "We could see tumour cells expressing cancer stem-cell markers and integrin-linked kinase located at regions with high collagen, which is used to estimate stiffness in a tumour," said Mei-Fong Pang, Researcher at the Princeton University.

The findings, published in the journal Cancer Research, suggested that stiffness and hypoxia cause integrin-linked kinase to behave abnormally, which in turn triggers cancer stem-cell formation. There are likely other features in tumours that cause cancer stem cells to form, but the findings indicate that stiff, hypoxic conditions and their effects on integrin-linked kinase are two of the most prominent ones. 

this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.
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https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes

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