e-SQUARE, January 2021

Features

Prostate Cancer !

Diabetes Diet !

Childhood Neglect !

Mystery of Virus !

Sunlight Exposure !

Estrogen Receptors !

New Products of SQUARE Pharmaceuticals Ltd.

EDITORIAL TEAM

OMAR AKRAMUR RAB

MBBS, FCGP, FIAGP,

P G Dip. Business Management

MAHFUZUR RAHMAN

MBBS, MBA

Rubyeat Adnan

MBBS, MPH

EDITORIAL

Dear Doctor,

Happy New Year 2021 !

Welcome to our online healthcare bulletin e- SQUARE !

In this issue, we focused on some interesting features like -
"Prostate Cancer !", "Diabetes Diet !", "Childhood Neglect !", "Mystery of Virus !", "Sunlight Exposure !", "Estrogen Receptors !".

In our regular feature, we have some products information of SQUARE Pharmaceuticals Ltd. as well.

Please send your feedback ! We always value your comments !

Click on to reply mode.

On behalf of the management of SQUARE, we wish you all a very happy, healthy and prosperous life.

Yours sincerely,

Editorial Team

Reply Mode : e-square@squaregroup.com

The views expressed in this publication do not necessarily reflect those of its editor or SQUARE Pharmaceuticals Ltd.

Prostate Cancer !
An unexpected, and novel, target for prostate cancer
Our biological or circadian clock synchronizes all our bodily processes to the natural rhythms of light and dark. It's no wonder then that disrupting the clock can wreak havoc on our body. In fact, studies have shown that when circadian rhythms are disturbed through sleep deprivation, jet lag or shift work, there is an increased incidence of some cancers including prostate cancer. Researcher analyzed human cancer data, the circadian factor CRY-1 was found to increase in late stage prostate cancers, and is strongly associated with poor outcomes. A common therapy for prostate cancer involves suppressing the male hormone androgen and/or the androgen receptor, as prostate tumors require androgens to develop and progress to advanced disease. Researchers found that CRY-1 is induced by the androgen receptor in prostate tumor tissue obtained from patients, thus explaining in part the high levels of CRY-1 observed in human disease. It is a clear indication of CRY-1's link to prostate cancer. Cancer treatments aim to damage the DNA in cancer cells and cause defects in repair mechanisms; eventually the cells self-destruct when the damage is severe. The researchers probed CRY-1's possible role in DNA repair in cultured cells, animal models and tissue harvested from prostate cancer patients. They first induced DNA damage by exposing cancer cells to radiation and found that CRY-1 levels became elevated, indicating that it was responding to this type of damage. They also found that CRY-1 directly regulates the availability of factors essential for the DNA repair process, and alters the means by which cancer cells respond to DNA damage. The findings suggest that CRY-1 may offer a protective effect against damaging therapies. The fact that CRY-1 is elevated in late-stage prostate cancer may explain why androgen-targeting treatments become ineffective at those later stages. Looking ahead, the team plans to explore how best to target and block CRY-1 and what other existing therapies may work synergistically to hinder DNA repair in prostate cancer cells. They also plan to study more circadian rhythm genes and determine how circadian disruption may affect cancer treatment. Researcher said that it’s been shown that circadian disruptions can affect efficacy of treatment, but also that aligning treatment with the body's natural rhythms or giving therapy at certain times of the day can be beneficial.
SOURCE: HealthDay, January 2021	Return to top

Diabetes Diet !
High doses of saccharin don't lead to diabetes in healthy adults
For those trying to live a healthy lifestyle, the choice between sugar and artificial sweeteners such as saccharin can be confusing. A new study led by researchers found the sugar substitute saccharin doesn't lead to the development of diabetes in healthy adults as previous studies have suggested. It's not that the findings of previous studies are wrong, they just didn't adequately control for things like underlying health conditions, diet choices and lifestyle habits. Non-caloric artificial sweeteners are often consumed as a substitute for dietary sugars, and saccharin is one of six artificial sweeteners approved by the Food and Drug Administration. The use of artificial sweeteners has increased dramatically over the past decade due to growing awareness of the negative health outcomes associated with consuming too much sugar, study authors noted. Previous studies elsewhere have suggested that consuming artificial sweeteners is associated with metabolic syndrome, weight gain, obesity and non-alcoholic fatty liver disease. These findings have raised concerns that consuming them may lead to adverse public health outcomes, and a lack of well-controlled interventional studies contributed to the confusion. Participants ingested capsules that contained the maximum acceptable daily amount of either saccharin, or lactisole (a sweet taste receptor inhibitor, or saccharin with lactisole or placebo every day for two weeks. The maximum acceptable daily amount of saccharin is 400 milligrams per day, which is far more than the average consumer would consume. The study excluded people with acute or chronic medical conditions or taking medications that could potentially affect metabolic function, such as diabetes, bariatric surgery, inflammatory bowel disease or a history of malabsorption and pregnant or nursing. Researchers also tested for 10 weeks the effects of even higher dose of saccharin in mice that genetically lack sweet taste receptors with the same results: the artificial sweetener didn't affect glucose tolerance, or cause any significant gut microbiota changes or apparent adverse health effects. Researcher said that when given the choice, artificial sweeteners such as saccharin are the clear winner based on all of the scientific information we currently have. Future research will study each FDA-approved sweetener individually to examine if there are any differences in how they're metabolized. Researchers will study these substances over a longer period of time to ensure they're safe for daily use.
SOURCE: Science Daily, January 2021	Return to top

Childhood Neglect !
Childhood neglect leaves generational imprint
Early life experiences can have an outsized effect on brain development and neurobiological health. New research is showing that those effects can be passed down to subsequent generations, reporting that the infant children of mothers who had experienced childhood emotional neglect displayed altered brain circuitry involved in fear responses and anxiety. These results show that our brain development is not only shaped by what happens in our own life, but is also impacted by things that happened to our parents before we were even conceived, said lead researcher. Researcher studied 48 Black mother-infant pairs starting in the first trimester of pregnancy. The mothers were also evaluated for current, prenatal stress levels, and for anxiety and depression. One month after birth, infants underwent a brain scan using resting-state functional magnetic resonance imaging, a non-invasive technology that could be used while the babies slept naturally. These remarkable results leverage our ability to image the brain and its functioning very early in life. The researchers focused on brain connections between the amygdala, which is central to processing fearful emotions, and two other brain regions: the prefrontal cortex and the anterior cingulate cortex. Both areas play a key role in regulating emotions. Babies whose mothers experienced childhood emotional neglect had stronger functional connections between the amygdala and the cortical regions. After controlling for mothers' current stress levels, the researchers found that the more emotional neglect a mother had experienced during her own childhood, the more strongly her baby's amygdala was connected to the frontal cortical regions. Physical abuse or neglect of the mother were not correlated with the stronger connectivity. The findings suggest that childhood emotional neglect has intergenerational effects on brain structure and function. The findings add to evidence of the intergenerational consequences of early life adversity, such as maternal neglect. Future studies that follow children longitudinally will help us understand the functional significance of these changes in brain function in terms of the emotional and social development of children of mothers who experienced early neglect.
SOURCE: Science Daily, January 2021	Return to top

Mystery of Virus !
Unravelling the mystery that makes viruses infectious
Researchers have for the first time identified the way viruses like the poliovirus and the common cold virus 'package up' their genetic code, allowing them to infect cells. Once a cell is infected, a virus needs to spread its genetic material to other cells. This is a complex process involving the creation of what are known as virions newly formed infectious copies of the virus. Each virion is a protein shell containing a complete copy of the virus's genetic code. The virions can then infect other cells and cause disease. What has been a mystery until now is a detailed understanding of the way the virus assembles these daughter virions. Researcher analysis suggests that the molecular features that control the process of virion formation are genetically conserved, meaning they do not mutate easily reducing the risk that the virus could change and make any new drugs ineffective. The study focuses on a harmless bovine virus that is non-infectious in people, Enterovirus-E, which is the universally adopted surrogate for the poliovirus. The poliovirus is a dangerous virus that infects people, causing polio and is the target of a virus eradication initiative by the World Health Organization. The enterovirus group also includes the human rhinovirus, which causes the common cold. Using a combination of molecular and mathematical biology, the researchers were able to identify possible sites on the RNA molecule that could act as packaging signals. Researcher were able to directly visualise this process the first time that has been possible with any virus of this type.
SOURCE: Science Daily, January 2021	Return to top

Sunlight Exposure !
Link between sunlight exposure and kidney damage
A new collaborative study from researchers reveals unexpected insights into how skin exposure to ultraviolet (UV) light can worsen clinical symptoms in autoimmune diseases such as lupus. Lupus, an autoimmune disease that can cause inflammation of the joints, skin, kidneys, blood cells, brain, heart and lungs, is caused when the immune system attacks its own tissue. Previous research has established that in up to 80 percent of lupus patients, sunlight exposure can trigger both local skin inflammation and systemic flares, including kidney disease. But little has been understood about the underlying mechanisms that drive this process. In the study, the researchers looked for markers of inflammation and injury in the skin, the blood, and the kidney at different time points following UV light exposure in mice & able to demonstrate that neutrophils not only infiltrated the UV light-exposed skin, but also dispersed throughout the circulatory system and migrated to the kidney. Interestingly, one subset of these neutrophils, the ones that researcher think are more damaging, first went to the skin that was exposed to the UV light and then turned around and went to the kidney. The investigators found that a single exposure of skin to UV light stimulates inflammatory and injury processes in the kidney, including transient proteinuria, even in normal, healthy mice. To be clear, normal, healthy mice don't get the clinical type of kidney disease that present in lupus patients. Researcher said that the mice recover and are fine afterwards & this subclinical injury may lead to pathologic consequences in the vulnerable setting of pre-existing inflammation in lupus patients, and lead to kidney disease flare after exposure to sunlight. Importantly, the inflammatory and injury markers they detected in the mouse kidneys following UV light exposure were very similar to the renal injury markers that are associated with more severe kidney damage in lupus patients. In addition, the exposure to UV light also triggered an immune response that is often expressed in most lupus patients the type 1 interferon response in both the skin and kidney.
SOURCE: Science Daily, January 2021	Return to top

Estrogen Receptors !
Estrogen receptors in mom's placenta critical during viral infection
Researchers identified a molecular mechanism that prevents a viral infection during a mother's pregnancy from harming her unborn baby. When a person becomes infected by a virus, their immune system sends out a chemical signal called type I interferon, which tells surrounding cells to increase their anti-viral defenses, including making more inflammation. This response helps to prevent the virus from copying itself and gives the adaptive immune system more time to learn about the new invader and begin to hunt it down. A pregnant woman who encounters a virus generates these same signals to protect herself, but if those signaling molecules and the resulting inflammation were able to cross the placenta and reach the fetus, they would lead to serious developmental abnormalities and even fetal death. But this generally doesn't happen, except for the Zika virus and a handful of other viruses known to replicate inside the fetus and harm it. The research team found a mechanism that protects the fetus from the harm the mother's immune response to a virus could cause. Having arrived at GPER1 as a possible candidate for this effect by a series of screens, the researchers found GPER1 receptors concentrated in the placenta, where the mother's blood supply passes oxygen and nutrients over to the fetus. Estrogen levels are much higher during pregnancy, making the GPER1 receptor even better able to suppress interferon signaling in the placenta and developing fetus. The researchers tried blocking this particular estrogen receptor in pregnant mice with a compound called G15. They found changes in the placenta during influenza A virus infection or G15 treatment, which led to slightly smaller mouse pups. But with both G15 and influenza virus present, the pups were dramatically smaller and many were stillborn. Researcher said that disable the GPER1 pathway, even normally benign maternal infections (like flu) will now cause major fetal developmental issues & the beauty of this system being concentrated around the baby is that it protects the fetus from inflammation, while leaving the rest of the mother's tissues more able to use interferon to fight the virus.
SOURCE: Science Daily, January 2021	Return to top

New Products of SQUARE Pharmaceuticals Ltd.

	Product	Emolent^TM Plus
	Generic Name	Light Liquid Paraffin + White Soft Paraffin + Glycerin
	Strength	10%+5%+10%
	Dosage form	Lotion
	Therapeutic Category	Emollient
	Product	Ulrif^TM
	Generic Name	Sucralfate USP
	Strength	1 gm/5ml
	Dosage form	Suspension
	Therapeutic Category	Antiulcerant
	Product	Telmilok^TM
	Generic Name	Telmisartan
	Strength	40 mg & 80 mg
	Dosage form	Tablet
	Therapeutic Category	Antihypertensive

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Healthcare online	Keeping you up-to-date
*VOL. 19 ISSUE: 1 January 2021*	Medical Services Department **SQUARE Pharmaceuticals Ltd.**