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CMS121 mitigates aging-related obesity and metabolic dysfunction

“[…] CMS121 applicability could be expanded from a geroneuroprotector drug to a metabolic drug […]” Credit: 2024 Dafre et al. “[…] CMS121 applicability…

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“[…] CMS121 applicability could be expanded from a geroneuroprotector drug to a metabolic drug […]”

Credit: 2024 Dafre et al.

“[…] CMS121 applicability could be expanded from a geroneuroprotector drug to a metabolic drug […]”

BUFFALO, NY- April 9, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 16, Issue 6, entitled, “CMS121: a novel approach to mitigate aging-related obesity and metabolic dysfunction.”

Modulated by differences in genetic and environmental factors, laboratory mice often show progressive weight gain, eventually leading to obesity and metabolic dyshomeostasis. The geroneuroprotector CMS121 has a positive effect on energy metabolism in a mouse model of type 2 diabetes. In this new study, researchers Alcir L. Dafre, Saadia Zahid, Jessica Jorge Probst, Antonio Currais, Jingting Yu, David Schubert, and Pamela Maher from Salk Institute for Biological Studies, National University of Sciences and Technology (NUST) and Federal University of Santa Catarina investigated the potential of CMS121 to counteract the metabolic changes observed during the ageing process of wild type mice.

“This comprehensive analysis aimed to further understand how CMS121 influences the metabolic landscape, paving the way for potential therapeutic applications beyond its established geroneuroprotective benefits.”

Control or CMS121-containing diets were supplied ad libitum for 6 months, and mice were sacrificed at the age of 7 months. Blood, adipose tissue, and liver were analyzed for glucose, lipids, and protein markers of energy metabolism. The CMS121 diet induced a 40% decrease in body weight gain and improved both glucose and lipid indexes. Lower levels of hepatic caspase 1, caspase 3, and NOX4 were observed with CMS121 indicating a lower liver inflammatory status. Adipose tissue from CMS121-treated mice showed increased levels of the transcription factors Nrf1 and TFAM, as well as markers of mitochondrial electron transport complexes, levels of GLUT4 and a higher resting metabolic rate. Metabolomic analysis revealed elevated plasma concentrations of short chain acylcarnitines and butyrate metabolites in mice treated with CMS121.

“The diminished de novo lipogenesis, which is associated with increased acetyl-CoA, acylcarnitine, and butyrate metabolite levels, could contribute to safeguarding not only the peripheral system but also the aging brain. By mimicking the effects of ketogenic diets, CMS121 holds promise for metabolic diseases such as obesity and diabetes, since these diets are hard to follow over the long term.”

 

Read the full paper: DOI: https://doi.org/10.18632/aging.205673 

Corresponding Authors: Pamela Maher, Alcir L. Dafre

Corresponding Emails: pmaher@salk.edu, alcir.dafre@ufsc.br 

Keywords: obesity, diabetes, geroneuroprotection, metabolic disorders, ketogenic diet

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About Aging:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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What is Grab? Southeast Asia’s post-Uber “everything app”

While you may never have heard of it, the Grab app has become as ubiquitous in southeast Asia as Uber, DoorDash, and Venmo are in the U.S. — and it…

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Grab, the Singapore-headquartered “Everyday Everything App,” is Southeast Asia’s answer to Uber, DoorDash, Instacart, and Venmo — all in a single platform. 

Best known for its ride-hailing and delivery services, the Grab app also offers a wallet feature that allows users to make payments online and in person, send money to family and friends, finance purchases over time, and even buy travel insurance.

In essence, Grab is (attempting to become) the go-to digital toolkit for everyday life in the eight countries in which it operates — currently, that’s Cambodia, Indonesia, Singapore, Malaysia, Myanmar, the Philippines, Thailand, and Vietnam.

The app has been called Southeast Asia’s answer to Uber, and, as of late 2023, Grab reportedly serves 35 million unique users each month according to the Business Times.

Much like Uber does in the U.S., Grab connects riders to drivers and diners to delivery people across eight countries in Southeast Asia.

Photo by Paul Lakatos/SOPA Images/LightRocket via Getty Images

Trading publicly in the United States on the Nasdaq exchange since its 2021 IPO, the company turned a profit for the first time during the fourth quarter of 2023 and shows no signs of slowing down.

Here’s what you need to know about Grab's features, its stock, and its ongoing quest to become Southeast Asia’s “one app to rule them all.”

Related: Surge pricing: Examples & how it works on Uber, Lyft, DoorDash & more

How did Grab become the Uber of Southeast Asia? A short history of the app

Grab was born in 2012 at Harvard Business School, the brainchild of Anthony Tan (CEO) and Tan Hooi Ling (COO), both Malaysian nationals who earned their MBAs there the year prior. The pair launched their mobile app — then called “My Teksi” — using a $25,000 grant from the school along with an unknown amount of personal capital. 

The purpose of the app was to connect taxi drivers with passengers via their smartphones in order to create a simple and orderly alternative to Malaysia’s then-chaotic (and sometimes unsafe, especially for female riders) ride-hailing environment.

In 2013, the company — by then called GrabTaxi — expanded, making its digital ride-hailing app available in the Philippines that summer, then in Singapore and Thailand before the year’s end. The next year, the company rolled out a fleet of 100 electric taxis in Singapore, expanded operations to major cities in Vietnam and Indonesia, and launched GrabBike, a ride-hailing service for motorbike rides.

Anthony Tan (CEO) launched grab with colleague Tan Hooi Ling (COO) in 2012 after the two graduated from Harvard Business School. 

Lionel Ng/Bloomberg via Getty Images

In 2015, the company launched GrabExpress as a package courier service. The following year, it rebranded (shortening its name to Grab and updating its logo) and introduced in-app messaging and translation for drivers and riders. It also created the GrabRewards program, through which users can earn points redeemable toward discounts on subsequent Grab services.

In 2017, the company launched GrabPay, its first financial technology offering, after acquiring an Indonesian payment company called Kudo. Next, it acquired Uber’s Southeast Asian assets and operations in early 2018, cementing Grab’s status as the dominant ride-hailing service in the region. 

As a result of this acquisition, which included Uber Eats, Grab added food-delivery services to its suite of offerings, first in Singapore and Malaysia, and then in the remainder of its market before the year’s end.

Related: The 5 most startling Chapter 11 retailer bankruptcies since 2020

As part of this deal, Uber received a 27.5% stake in Grab, and Uber CEO Dara Khosrowshahi joined the company’s board. So, the American-based ride-hailing and delivery giant now has a vested interest in seeing Grab succeed in its own market. Also as part of this 2018 acquisition, Grab agreed to go public by March 2023, a promise it kept with a little over a year to spare.

Business Insider reported the same year that Grab had become Southeast Asia’s first “decacorn” after securing more funding than any other tech startup in the region during the three years prior. (Unicorns are privately held companies worth more than $1 billion, while “decacorns” are privately held companies worth over $10 million.)

The company continued to make acquisitions in the fintech space, gradually expanding its in-app financial offerings to include money transfers, payments to merchants, microloans, insurance services for drivers and passengers, and buy-now-pay-later programs.

Anthony Tan (CEO) and Tan Hooi Ling (COO) are pictured here celebrating the company's 2021 IPO on the Nasdaq stock exchange. 

Bloomberg/Getty Images

By the time it went public on the U.S. stock market via a SPAC merger with Altimeter Growth Corp., the company had built a vast network of partnerships that allowed customers to hail car and motorbike rides, book travel, order food, pay for goods and services, send and receive money, and even obtain travel insurance policies.

In December 2021, Grab shares opened at $13.06 during the company’s first day trading on the Nasdaq, but they tumbled to around half that by the end of the day. Shares continued to fall, and for the next two years, they bobbed up and down in the $2.80 to $3.80 range.

In the fourth quarter of 2023, however, Grab moved into the black for the first time, posting a profit of $11 million on revenue of $653 million, up 30% from the 2022 fourth quarter. 

So, what’s next for the Uber-backed “everything app?”

Related: A History of Reddit: From “front page of the internet” to billion-dollar valuation

Is Grab stock a buy? 

The market has known since late February 2024 that Grab became profitable during 2023’s final quarter and that it was initiating its first-ever share repurchase program (both of these are usually positives for a stock). That news, however, didn’t seem to do much to bolster the company’s stock price, which sat at around $3.16 then and hadn’t moved much by early April.

The company’s first-quarter 2024 earnings call is set for May 16, and any guidance the company issues on the call could be the catalyst that pushes the stock out of its limbo. 

As of this article's last update, company insiders held about a quarter of Grab's stock, while institutional investors — including Morgan Stanley, Blackrock, Invesco, and Bank of America — held just shy of 55% percent. Short interest stood at 2.73%, indicating largely positive sentiment. 

Tipranks listed Grab as a "strong buy" based on 10 analyst ratings with an average 12-month upside of about 34%.

During the company’s last earnings call, CEO Anthony Tan said that Grab has grown to become the “largest on-demand platform in the region at a scale that is over 3x larger than [its] next-closest competitor.” 

He also noted that, as pandemic-related travel hesitation has waned, the company’s “mobility revenues also increased by 26% YoY in Q4 and 36% YoY for the entire year, driven by an increase in tourist ride-hailing demand.”

During the call, Tan mentioned that the brand is increasing its focus on its travel segment. The travel business offers hotel booking and travel insurance services (more on these below), as non-local travelers tend to spend more than local customers in the markets where Grab operates.

All signs point to continued growth, but growth is expensive, so whether the company will continue to post profits in subsequent quarters will depend on how much it spends on acquisitions and partnerships vs. how much it leverages its current assets.

Related: Boeing's turbulent descent: The company’s scandals & mishaps explained

Grab’s services and features explained

Because Grab operates in hundreds of cities across eight different countries, the services it offers vary by location. So, some of the features explained here may not be available in all markets.

For instance, Grab users in Vietnam, where motorbikes are ubiquitous, can order motorbike rides as a cheaper alternative to hiring a car, whereas in Singapore, where motorbikes are less popular, only car taxi rides are available.

Ride-hailing

Taxi-hailing was Grab’s first offering when it launched in Malaysia in 2012. The company’s mobility arm remains one of its most important, although it now ranks second to delivery in terms of revenue.

Functionally, Grab rides work much like those booked through Uber or Lyft in the U.S. Grab users can enter their destination and book taxi rides through the app with the cost shown up-front. Those willing to wait longer for a ride, share a car with other riders, or ride on the back of a motorbike can access lower fares.

All riders can view drivers’ details and ETA, and message drivers with instructions (the app can translate these messages if the rider and driver use different languages). Larger vehicles, pet-friendly cars, cars with booster seats for children, and luxury vehicles are also available at various price points.

Grab's food delivery service works much like Uber Eats or DoorDash does in the U.S.

LILLIAN SUWANRUMPHA/Getty Images

Delivery services

Grab offers three types of delivery services: food, mart, and express. Together, these services account for more revenue than the company’s ride-hailing services.

GrabFood

Grab’s food-delivery feature is quite similar to DoorDash and Uber Eats. Customers can browse the menus of a variety of restaurants, ranging from street carts to fine dining, and order food for delivery, pick-up, or dine-in. Deliveries can be immediate or scheduled, and in-app discounts, coupons, and rewards are sometimes made available.

GrabMart

Grab’s mart delivery feature is similar to American apps like Instacart and GoPuff. Users can browse the wares of partner grocery, pharmacy, and convenience stores and order anything from food staples to toiletries. Deliveries can scheduled ahead of time or placed on an ASAP basis.

GrabExpress

GrabExpress is the company’s courier feature, which offers the types of services bike messengers provide in large American cities. A user requests a delivery and then hands off their parcel to a Grab partner, who immediately totes it to its destination, providing photographic proof of delivery upon completion.

This service can be used to send anything from a confidential single-page document to a 50 kg (110 lb) package, and all deliveries are automatically insured up to $500 (additional protection of up to $2,000 can be purchased for higher-value deliveries).

GrabPay allows users to pay for purchases online and in person using funds in the app's digital wallet. 

Bloomberg/Getty Images

Financial services

Since around 2017, Grab has been expanding the financial side of its app via strategic acquisitions and partnerships with fintech companies. Its financial products vary depending on location, but most center around the GrabPay Wallet.

GrabPay Wallet

The GrabPay Wallet is a cashless payment system Grab customers can use to pay for Grab services, pay bills, send money to others, and make purchases online and in-person at merchants that accept GrabPay.

The GrabPay Wallet’s functionality is similar to that of Paypal or Apple Pay, and by using it, customers accumulate GrabRewards points that can be redeemed toward any of the services the Grab app offers.

Rider and driver insurance

Grab riders are automatically insured up to $20,000 in personal accident coverage whenever they hail a car or bike, and supplementary coverage of up to $100,000 can be purchased for an additional $0.30 per ride.

Grab drivers are also insured automatically up to $20,000 for accident-caused death or disability and up to $2,000 for accident-caused medical expenses. 

Third-party liability insurance also covers drivers up to $200,000 for injury or property damage to others. Driver insurance also pays out up to $200 per day for 60 days of hospitalized medical leave or 14 days of non-hospitalized medical leave.

Travel

Grab also offers some in-app solutions for non-local travelers, although these are still somewhat limited.

Travel insurance

Grab users who are traveling can use the app to purchase travel insurance that covers things like medical expenses, delays, and lost luggage. Users enter basic information like their destination and trip duration, and the app provides an instant quote, with daily premiums starting at around $4.

Hotel booking

Grab users can book stays at millions of hotels directly through the Grab app, sometimes with Grab-exclusive discounts, earning Grab rewards as they do so. 

Related: Bitcoin's history: A timeline of the crypto's milestones ahead of halving event

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History of Crypto: DeFi revolution during a global crisis

Analyzing the impact of the pandemic on crypto and the explosive growth of DeFi, including Bitcoin’s third halving and the rise of NFTs.

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Analyzing the impact of the pandemic on crypto and the explosive growth of DeFi, including Bitcoin’s third halving and the rise of NFTs.

The COVID-19 pandemic wreaked havoc on human lives and the world economy when it broke out in early 2020. The crypto world was battered as well, with the cryptocurrency market plummeting in March of that year. Bitcoin (BTClost 52% of its dollar value in a day, and Ether (ETH) lost 43%, shaking up decentralized finance (DeFi) as it fell.

The resulting lockdowns had a slower but more profound effect on crypto. As the world became housebound, screen time rose steadily, and interest in cryptocurrency soared, along with market capitalizations. Soon, emerging technologies were undergoing development and implementation at a pace previously unseen.

The first steps in DeFi were taken in 2017 with the development of smart contracts on the Ethereum blockchain. MakerDAO and Compound were early market leaders. In June 2020, Compound introduced yield farming, also known as liquidity mining, a method of arbitrage that shifted crypto assets to attain the highest interest, fees and rewards. It is now common practice.

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The Media Hates It, But It’s Time to Go All In on This Kind of Stock

Investors Alley
The Media Hates It, But It’s Time to Go All In on This Kind of Stock
It’s time. It’s time to start buying real estate. Commercial…

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Investors Alley
The Media Hates It, But It’s Time to Go All In on This Kind of Stock

It’s time.

It’s time to start buying real estate.

Commercial real estate.

That’s right, the asset class everybody hates and thinks will collapse the banking system, the government, and everything except companies that make AI-related semiconductor chips.

The media hates it.

The clickbait hunters love the stuff because it is so easy to craft doom-and-gloom marketing measures around empty offices and defaulted loans.

But the truth is, now is the perfect time to start buying. Here’s why…

Don’t get me wrong.

We have not seen the end of the ugly headlines by any stretch of the imagination.

Downtown office towers are still going to have some problems.

Some of the overleveraged ones will still be working their way through the stages of foreclosure.

Most are still in disbelief, with bargaining, plotting, pleading, begging, and throwing the keys at the lender’s head in disgust still to come.

We could have months of ugly headlines from the office sector.

Most troubled properties will be big city center city towers in gateway markets.

Class B and C apartments may have some problems as well.

Is it really the bottom? The absolute bottom in real estate?

I doubt it. I have never picked an absolute top or bottom; I suspect that will not change anytime soon.

We could see lower prices before the markets reverse and go higher.

It may be months, or even a year or more, before the markets start to get excited about commercial real estate again.

I prefer it that way.

The longer it takes, the more time I have to find and buy quality real estate-related opportunities.

I do not know when the absolute bottom in real estate will be.

Here is what I do know:

Big and tech companies are starting to push for workers to return.

The vast majority of people will not quit a good-paying job to avoid commuting.

Class A offices are filling up as tenants use the current market weakness to upgrade.

The same flight to quality is happening in cities large and small when it comes to apartments and rental housing.

The migration to states with warm weather and lower taxes will continue.

People with good jobs and full bank accounts will still go shopping.

The very best malls, both indoor and outdoor, will continue to thrive

We will still go to pharmacies, grocery stores, and other necessary retail locations.

Our national fascination and attachment to “stuff” will keep the self-storage facilities full.

People who have discovered and fully embraced the lazy delights of shopping from home will keep warehouses in high demand.

The lessons of the pandemic’s early days will continue to drive demand for new local warehouse space for many retailers.

Some commercial real estate loans will default. Most will not.

So far, I am finding opportunities for my members and myself in high-quality REITs, real estate, corporate debt, preferred stocks, closed-end funds, homebuilders, and real estate services companies.

I strongly prefer opportunities that throw off a lot of cash.

Cash coming in the door makes it much easier to wait for prices to settle down and begin to head higher again.

While only a few people are moving to buy real estate right now, I am not entirely alone.

Jonathan Gray, the President of Blackstone, recently said, “The perception is so negative, and yet the value decline has occurred, so when you get into this bottoming period, that’s when you want to move.”

He added “As investors, sometimes, one of the risks is that you miss it by being overly cautious, and I think now is probably a good time before rates come down.”

Blackstone is one of the world’s largest owners of commercial real estate properties. I think they might know what they are talking about regarding the opportunity I see developing in commercial properties.

I will hold most of the assets and companies I am buying today until everyone wants to own real estate, and real estate speculation promotions have replaced all the options trading ads.

There are a few world-class assets that I suspect I will hold forever.

Many debt-related investments will be sold at a premium when real estate is upgraded, or the Fed cuts rates.

We could see a double whammy that delivers a two-for-one pop in the price of real estate-related debt over the next year or two.

I don’t know when the exact bottom will occur in real estate.

However, I am absolutely certain that in a few years, my readers and I will be very happy with the high-quality, high-grade real estate investments we are making today.

Biden Needs This ‘Dirty Oil’ Stock For His $4.5 Trillion Revolution

This company has a stranglehold on 25% of America’s energy… and thanks to a rare situation happening now… it could skyrocket past its 2,177% all-time performance record… while paying your bills for life! Click here for the full details.

 

The Media Hates It, But It’s Time to Go All In on This Kind of Stock
Tim Melvin

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