Gary‘s Daily Health News - Vol. 12

Korean scientists emphasize the health benefits of ginseng

Pusan National University (South Korea), September 16, 2021

Ginseng, a widely popular superfood, has long been used in traditional medicine. The health benefits of ginseng are largely attributed to compounds called ginsenosides, which are present in the roots, stems, and leaves of the plant. Ginsenosides are known to prevent inflammation, diabetes, and cancer, and can also help control blood cholesterol levels and reduce aging.

Although there are 13 known species of ginseng, Korean ginseng—which contains the highest number of ginsenosides—is not commonly found in nature. Moreover, of the two types of ginsenosides, the more effective variety—the minor ginsenosides—accounts for only 20% of the total ginsenoside content in ginseng. As a result, the supply of ginsenosides is insufficient to meet the high demand in the nutraceutical and pharmaceutical industries. In order to improve ginsenoside production, a one-stop resource with consolidated information from previous ginsenoside studies is required, but such a resource is currently unavailable.

A team of researchers led by Dr. Ravi Gupta from Kookmin University and Dr. Sun Tae Kim from Pusan National University, Korea, embarked on a journey to address this gap. In their recent review published in Critical Reviews in Food Science and Nutrition, they compiled a vast amount of data from a large number of ginsenoside studies across multiple fields, including botany, biochemistry, genetics, and drug research.

In addition to providing an overview of the different types and sources of ginsenosides, this review highlights several opportunities for improving ginsenoside production, both in the natural sources, as well as in synthetic biosystems. First, it discusses how major ginsenosides can be converted to the more effective minor type using chemical and enzymatic treatments as well as microbial action. Subsequently, it focuses on how treatments such as water restriction, light stress, gamma radiation, and the administration of plant hormones like jasmonic acid can enhance the ginsenoside content of ginseng.

Finally, the review provides a detailed summary of the biochemistry underlying ginsenoside synthesis in plants as well as its regulation at the gene level. “Understanding and identifying the genes and pathways involved in ginsenoside production can help us develop plants containing high levels of ginsenosides. The identified genes can also be inserted into other organisms that do not make ginsenosides to create artificial systems like ginsenoside-producing yeasts,” explains Dr. Gupta, adding that such strategies would be essential for large-scale ginsenoside production. 

This review is the first of its kind to focus on ginsenosides on a wide scale. “This was a mammoth challenge, but we strongly believe that our efforts will bear fruit. Our work cements together all the research that has been conducted in the past, and we hope that in the future, scientists will capitalize on it and develop new ways to meet the global demand for ginsenosides,” according to Dr. Kim.

This work by Dr. Gupta, Dr. Kim, and their team is an important tool in further improving the industrial potential of a natural food that is a trove of nutrients necessary for healthy living. This is indeed great news for health enthusiasts the world over!

 

Study reveals how saline solution can inhibit replication of SARS-CoV-2

The use of a hypertonic solution of sodium chloride at 1.1% reduced viral replication by 88% in tests involving infected lung cells 

University of San Paulo (Brazil), September 21, 2021

Researchers at the University of São Paulo (USP) in Brazil have shown that a hypertonic saline solution inhibits replication of SARS-CoV-2, the virus that causes COVID-19, and have elucidated the biochemical mechanism involved. An article reporting the research is published in ACS Pharmacology & Translational Science. The study was performed in the laboratory using human epithelial lung cells infected with the virus.

If the strategy proves effective in clinical trials, it could contribute to the development of novel prophylactic interventions to prevent COVID-19 or even treatments for the disease.

“Given the gravity of the pandemic, we believe it would be important to extend this line of research by conducting clinical trials designed to verify the efficacy of using a spray with hypertonic sodium chloride [NaCl] saline as a form of prophylaxis, helping to stop the virus from spreading within the infected organism and reducing the likelihood of more severe inflammation,” said Cristiane Guzzo, last author of the article and a researcher at the university’s Biomedical Sciences Institute (ICB-USP).

The study was supported by FAPESP. Edison Durigon, Professor of Virology at ICB-USP, and Henning Ulrich, at the Institute of Chemistry (IQ-USP), also participated.

Although the evidence suggests the use of saline inhibits viral replication, it does not afford full protection against infection, let alone a cure. “It’s very simple and cheap. It’s already used prophylactically against other respiratory diseases, and it could minimize the severity of COVID-19 by reducing viral load. It could be added to safety protocols without replacing the use of face coverings, social distancing and vaccination,” Guzzo said.

The right concentration

By comparing different concentrations of the product, the researchers found that a 1.5% NaCl solution completely inhibited viral replication in Vero cells. In human epithelial lung cells, a 1.1% solution was sufficient to achieve 88% inhibition. Vero cells are derived from kidney epithelial cells extracted from an African green monkey, and widely used as a model for studying SARS-CoV-2.

Hypertonic saline is already adopted prophylactically to manage cases of influenza, bronchiolitis, rhinitis, sinusitis, and other respiratory disorders. A spray is sufficient for the upper airways, while a nebulizer is needed to reach the lungs. These interventions can minimize the symptoms of such diseases, but the mechanisms underlying their effects are poorly understood.

“Our explanation of this intracellular response to the hypertonic solution was basic science but the findings of the study have evident applications in healthcare and clinical approaches to the management of various respiratory diseases,” Ulrich said. “What we observed with regard to SARS-CoV-2 is likely to apply to other viruses as well, since the mechanism concerned is part of the host cell’s response to infection.”

No energy

To grasp the mechanism involved, it is useful to bear in mind that viruses use elements of the host cell such as proteins and energy sources to replicate their genetic material and invade other cells and organs. “We discovered that NaCl doesn’t interfere with interaction between the SARS-CoV-2 spike protein and the ACE-2 receptor used by the virus to invade cells, but the saline does affect the post-infection viral cycle,” Guzzo said.

In an earlier article, published in The Journal of Physical Chemistry Letters, Guzzo and colleagues showed how interaction between the spike protein and ACE-2 receptor survived different concentrations of NaCl. “The virus probably evolves so as to compensate for fluctuations in ionic strength and maintain an effective medium for cell invasion,” she said.

When NaCl molecules enter a cell, the membrane surrounding the cytoplasm is polarized owing to an increase in sodium ions (Na+). As a result of this energy imbalance, a large amount of the cell’s potassium (K+) is ejected to restore a balance of charges in the membrane (this mechanism is known as the sodium-potassium pump). 

Saturation due to the sodium-potassium pump makes the cell expend ATP (adenosine triphosphate), one of the main sources of energy for cellular processes. Consumption of ATP for cellular depolarization prevents the virus from using it to replicate.

“Cells have to get rid of sodium via the sodium-potassium pump, and this uses up their energy store, so there’s no ATP left for viral replication,” Ulrich explained.

The study also showed that the salt does not affect mitochondrial activity. Mitochondria are dynamic organelles involved in cellular respiration and ATP creation, as well as other metabolic processes. “At these concentrations, the salt doesn’t damage the cell. We observed that mitochondria remained healthy throughout the process,” Guzzo said.

In the study, the researchers suggest that the use of hypertonic saline could be tested in two ways. One is a nasal spray for prophylaxis of the airways, the main gateway for SARS-CoV-2 to enter the organism. “This type of spray can be found in any pharmacy and could be used prophylactically by front-line health workers or other people who are highly exposed to the virus. If its efficacy is confirmed in clinical trials, it could reduce viral replication in the nose and throat,” Guzzo said.

The other strategy they propose is nebulizing the saline into the lungs. In this case, the right concentration of NaCl is essential, and the efficacy of the method can be assessed only in clinical trials involving COVID-19 patients. It is worth recalling that hypertonic saline nebulization is already used to treat children with bronchiolitis, for example.

In the case of respiratory syncytial virus (RSV), the most common cause of bronchiolitis, hypertonic saline is known to reduce infection and inflammation in cultured human respiratory epithelial cells.

“It’s not a single solution, and it would have to be used in the first few days after infection,” Guzzo said. “Reducing viral replication means reducing the severity of the disease and the inflammatory response. COVID-19 is a complex disease, comprising the viral replication stage, which hypertonic saline could treat, and then systemic inflammation, which is far more extensive. This second stage can be intense and lead to a number of complications in different organs.”

 

Link between inflammation and pancreatic cancer development uncovered

University of Texas MD Anderson Cancer Center, September 16, 2021

A new discovery from researchers at The University of Texas MD Anderson Cancer Center has clarified the long-established connection between inflammation and pancreatic cancer development. According to the study published today in Science, pancreatic cells display an adaptive response to repeated inflammatory episodes that initially protects against tissue damage but can promote tumor formation in the presence of mutant KRAS.

The authors demonstrated that mutant KRAS—which is found in roughly 95% of all pancreatic cancers—supports this adaptive response, leading to selective pressure to maintain the cancer-causing mutation.

"We discovered that a single transient inflammatory event induced long-term transcriptomic and epigenetic reprogramming of epithelial cells that cooperated with oncogenic KRAS to promote pancreatic tumors long after the inflammation was resolved," said corresponding author Andrea Viale, M.D., assistant professor of Genomic Medicine. "In the setting of repeated pancreatitis, KRAS mutations can be acquired early on to limit tissue damage, suggesting the existence of a strong evolutionary pressure to select mutated cells and providing a possible explanation for the nearly universal presence of mutant KRAS in pancreatic cancers."

Clarifying the connection between inflammation and cancer

Inflammation has long been linked to tumor development in several cancer types, but the specific reasons behind this connection were previously unclear. The research team, led by co-first authors Edoardo Del Poggetto, Ph.D., postdoctoral fellow, and I-Lin Ho, graduate student in the Viale Laboratory, sought to study the effect of pancreatitis—a condition of inflammation in the pancreas linked with a higher risk of pancreatic cancer—on pancreatic epithelial cells.

The researchers stimulated transient inflammation in a model system of inducible KRAS-driven pancreatic cancer. Inflammation caused immediate pathological changes in pancreatic cells, but they resolved within one week. However, activation of KRAS even months following the resolution of inflammation resulted in accelerated tumor formation compared with controls, suggesting that inflammation drives long-term changes in epithelial cells that cooperate with mutant KRAS to promote cancer development.

Deep molecular analysis of epithelial cells following a single inflammatory event demonstrated substantial reprogramming of gene expression and epigenetic regulation that persisted long after recovery of the tissue damage, a process the researchers termed "epithelial memory." This cellular reprogramming activated pathways related to cell survival, proliferation and embryonic development, which are similar to pathways active during cancer development.

Epithelial memory enables rapid response to limit tissue damage during recurrent pancreatitis

The cellular reprogramming caused by inflammation also facilitated the acquisition of acinar-to-ductal metaplasia (ADM), a reversible process in which pancreatic acinar cells acquire features of ductal cells. Acinar cells are responsible for producing and secreting digestive enzymes, while ductal cells are responsible for delivering those enzymes to the small intestine. ADM, a process that normally occurs in response to pancreatic damage, is thought to be a pancreatic cancer precursor.

In the context of epithelial memory, repeated inflammatory episodes resulted in the rapid and extensive appearance of ADM with minimal signs of cellular damage, suggesting that the cellular reprogramming protects the pancreas against an accumulation of tissue damage. These findings also clarify that ADM is not a cancer precursor state, but rather an adaptive response to inflammation.

Previous research has shown that KRAS mutations can induce and stabilize ADM. Here, the authors demonstrated that induction of mutant KRAS during repeated inflammations resulted in more pronounced ADM and virtually no tissue damage. Thus, the authors predict that cells undergoing inflammation would have a strong positive selection for KRAS mutations or other alterations that stimulate ADM and limit damage accumulations.

"We are working to better understand how cells maintain the epithelial memory we observed, but our data suggest that KRAS initially has a beneficial role during pancreatitis," Ho said. "There may be similar phenomenon in other cancers with universal driver mutations, where there is a strong pressure to select those mutations based on some purpose unrelated to cancer development."

The research team now is working to develop strategies to stimulate ADM in the pancreas while countering the selection pressure for mutated KRAS. If effective, the work may offer new treatments for pancreatitis that could also prevent pancreatic cancer development.

 

Cure For Aids? Bee Venom Destroys HIV Cells, Finds Study

Washington University School of Medicine, September 18, 2021

 

Ever wondered why bees are so important to our survival? One of the thousands of reasons is the fact that they help to cure AIDS.

Scientists from Washington University School of Medicine in St. Louis, have found that by poking holes in the protective envelope surrounding HIV and other viruses, melittin – a toxin found in bee venom – kills the human immunodeficiency virus (HIV) while leaving the body unharmed. This breakthrough could lead to drugs that are immune to HIV resistance; development of an anti-HIV vaginal gel that may prevent the spread of HIV; as well as possible treatments for existing HIV infections (In 2015, nearly 40 million people were living with the lethal virus globally).

 

Dr Joshua L. Hood, a research instructor in medicine at Washington University, remarked:

Melittin on the nanoparticles fuses with the viral envelope. The melittin forms little pore-like attack complexes and ruptures the envelope; stripping it off the virus… We are attacking an inherent physical property of HIV. Theoretically, there isn’t any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus.

 

In laboratory tests, the researchers fused melittin to nanoparticles, which are physically smaller than HIV. Since “protective bumpers” were earlier added to the nanoparticles’ surface, the melittin-loaded nanoparticles simply bounced off when they came into contact with normal cells. But when they contacted the HIV, the melittin-loaded nanoparticles ruptured the virus’ protective coat and killed it.

 

Hood says, as this thrilling anti-viral therapy attacks an essential part of the virus’ structure, it has the potential to prevent the HIV infection, to stop initial infection, as well as to cure existing infections, especially those that are drug-resistant.

 

Our hope is that in places where HIV is running rampant, people could use the vaginal gel as a preventive measure to stop the initial infection… We are attacking an inherent physical property of HIV. Theoretically, there isn’t any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus.

 

The basic particle that we are using in these experiments was developed many years ago as an artificial blood product. It didn’t work very well for delivering oxygen, but it circulates safely in the body and gives us a nice platform that we can adapt to fight different kinds of infections.

 

Could the bee venom-based anti-viral therapy be a game-changer for stopping the spread of AIDS, especially for couples in which one partner is infected with HIV and the other is not? Hood noted:

 

We also are looking at this [therapy] for couples where only one of the partners has HIV, and they want to have a baby. These particles by themselves are actually very safe for sperm, for the same reason they are safe for vaginal cells.

 

The study, published in the journal Antiviral Therapy, came after researchers from Johns Hopkins Children’s Center, the University of Mississippi Medical Center and the University Of Massachusetts Medical School reported that a Mississippi baby with HIV had apparently been cured, only after he received antiretroviral therapy within 30 hours of birth.

 

Recently, researchers at Philadelphia’s Temple University employed CRISPR/Cas9 gene editing technology (first developed in 2012) to remove HIV-1 DNA out of the human genome; and when they reintroduced HIV to the edited genomes, the cells were no longer infected with the lethal virus. The study authors observed:

These observations suggest that a cure strategy for HIV-1 infection should include methods that directly eliminate the pro-viral genome from the majority of HIV-1-positive cells, including CD4+ T-cells, and protect cells from future infection, with little or no harm to the host. The results point toward this approach as a promising potential therapeutic avenue to eradicating HIV-1 from T reservoir cells of host patients, to prevent AIDS re-emergence.

 

 

Vegetable Compound Shows Promise Against Diabetic Kidney Disease

AlMaarefa University (Saudi Arabia), September 9, 2021

A compound that occurs in watercress and other cruciferous vegetables, phenethyl isothiocyanate (PEITC), has shown a potential benefit against diabetic nephropathy, according to research on rodents presented at the American Association for Anatomy annual meeting, held during Experimental Biology 2021.*

“Diabetic nephropathy is a serious microvascular complication of diabetes mellitus and the major cause of end-stage renal disease,” Mohamed El-Sherbiny, PhD, and colleagues wrote.

Previous research has indicated that a vegetable compound known as sulforaphane that is related to PEITC reduces diabetes-associated kidney damage. For the current study, the research team evaluated the effects of PEITC in a rat model of diabetic nephropathy. The animals were given 3, 10 or 30 milligrams per kilogram PEITC for eight weeks. Kidney function, inflammation, oxidative stress, total antioxidant capacity, antioxidant enzyme levels, protein glycation and kidney structure were assessed at the beginning and end of the treatment period.

Phenethyl isothiocyanate administration was associated with improved kidney function, oxidant/antioxidant balance, inflammation and protein glycation, with higher doses associated with greater results. Kidney structure was also better preserved in association with PEITC. 

"Phenethyl isothiocyanate seems to manage one of the most serious and painful diabetic complications,” remarked Dr El-Sherbiny, who is a postdoctoral fellow at AlMaarefa University in Riyadh, Saudi Arabia. “Phenethyl isothiocyanate is naturally present in many dietary sources, importantly watercress, broccoli, turnips and radish.”

"Our study provides, for the first time, evidence that PEITC might be effective as a naturally occurring agent to reverse serious kidney damage in people with diabetes," he announced. "Our study introduces mechanistic evidence of how PEITC might manage kidney injury associated with diabetes by targeting multiple interconnected pathways involved in diabetic nephropathy, including inflammation, glycation and oxidative status."

 

 

 

High-calcium, low-lactose diet may reduce risk of ovarian cancer in African-American women

Rutgers Cancer Institute of New Jersey, September 16, 2021 

 

Research from Rutgers Cancer Institute of New Jersey and and other U.S. health and academic institutions shows a diet high in calcium and low in lactose may reduce the risk of ovarian cancer in African-American women. The work, which appears in the latest edition of the British Journal of Cancer, also found sun exposure in the summer months may reduce the risk of developing the disease in this population.

 

Ovarian cancer is the fifth leading cause of cancer death among women in the U.S., according to the National Cancer Institute. And while five-year survival rates for this disease have improved in Caucasian women from 35 percent to 46 percent, rates decreased in African-American females during this period from 42 to 38 percent (Howlader, et al., 2005). Previous studies have revealed positive associations between dairy consumption or lactose intake with the risk of ovarian cancer, and other studies have not. Given the populations in these previous works were primarily of European ancestry, Rutgers Cancer Institute investigators and their collaborators wanted to focus on the African-American population.

 

The associations were evaluated among participants in the African-American Cancer Epidemiology Study, which is an ongoing population-based case-control study of ovarian cancer in African-American women in 11 states including NewJersey. African-American females aged 20 to 79 years old with newly diagnosed invasive epithelial ovarian cancer were deemed eligible case participants. Healthy control participants were self-identified African-American women and were selected using random-digit phone dialing. Eligible for analysis were 490 case participants and 656 control participants who completed a phone questionnaire regarding various lifestyle factors including how many dairy products they consumed each week and how much time they spent in the sun.

Investigators found that both lactose intake and consumption of whole milk were significantly associated with an increased risk of ovarian cancer risk in African-American women, while skim and low-fat milk were not. No association was found for cheese or yogurt products. Calcium intake, whether through food and/or supplement, was associated with a decreased risk of disease. While researchers found no association between dietary and supplemental vitamin D intake and ovarian cancer risk, they noticed that fewer than 20 percent of African-American women in the study achieved the recommended daily vitamin D intake of at least 600 IU (or 800 IU if older than 70 years of age).

 

Results also showed that increased sun exposure may reduce ovarian cancer risk in this population. While separate research (Holick, 2011) shows Caucasian women need only five to 15 minutes of mid-day sun during spring, summer and fall to achieve an adequate amount of vitamin D production, African-American women need exposure five to 10 times longer due to their skin pigment. The current study's lead author, Rutgers Cancer Institute researcher Bo "Bonnie" Qin, PhD, is aware of the risks for skin cancer. "Because the benefits of increased sun exposure in African-American women may be offset by an increased risk of skin cancer, a combination of moderate sun exposure coupled with sufficient vitamin D intake from diet and supplements may be a safer solution for adequate vitamin D levels," notes Dr. Qin.

 

The study's senior author Elisa Bandera, MD, PhD, who is co-leader of the Cancer Prevention and Control Program at Rutgers Cancer Institute, notes this research adds to the scarce literature on causes of ovarian cancer in the African-American population. "Given that we were able to recruit a large sample of healthy African-American women and those with ovarian cancer from various geographic regions with diverse socioeconomic and lifestyle characteristics, we are able to generalize our findings to the African-American population," says Dr. Bandera, who is also a professor of medicine at Rutgers Robert Wood Johnson Medical School and a professor of epidemiology at Rutgers School of Public Health. "Considering there is no effective screening tool for ovarian cancer and that African-American patients have poor survival rates with this disease, prevention through lifestyle or dietary modifications is critical."