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Reviewed by Emily Henderson, B.Sc. Mar 17 2023

Tyrosine kinase inhibitors are a type of targeted cancer medicine that can attack specific types of cancer cells and prevent them from multiplying. Although these inhibitors, called TKIs, can be very useful in fighting certain cancers, they also cause serious inflammatory side effects that limit their use. A Japanese research team has discovered the underlying mechanism that causes this inflammation. This study revealed the underlying mechanism by which the TKIs cause inflammation, and therefore provides the molecular basis that is essential to overcome the inflammatory-based side effects."

Atsushi Matsuzawa, Professor at the Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University

The team's findings were published in The Journal of Immunology on February 6, 2023.

These TKIs are essential anticancer drugs. However, the use of TKIs frequently initiates inflammation in the body, such as the lung disease interstitial pneumonitis. From their earlier studies, the team had learned that a representative TKI called Gefitinib (GF) causes lung inflammation. GF is a helpful cancer medication used in treating certain breast, lung, and other cancers. It works by targeting the epidermal growth factor receptors. When the GF is used to treat the cancer, it can also cause inflammation in the patient's lungs, through the NLRP3 inflammasome. The NLRP3 inflammasome is part of the body's immune system and plays an important role in innate immunity. But when the NLRP3 inflammasome is improperly activated, it can contribute to the development of a wide range of inflammatory diseases.

Until now, scientists have not fully understood why the NLRP3 inflammasome is activated, but the evidence seems to point to mitochondrial dysfunction. When mitochondria are healthy, they work like batteries, producing energy in the body's cells. Mitochondrial dysfunction happens when the mitochondria do not work as they should because of disease. In their earlier study, the team learned that the GF activated the NLRP3 inflammasome through mitochondrial damage that led to the interstitial pneumonitis in patients. However, they had not understood how GF initiates the mitochondrial damage and whether or not other TKIs also shared this mechanism. Cancer Research eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy

To conduct their study, the team looked at the tyrosine kinases, those enzymes that work as a kind of "on" and "off" switch in many of the cells' functions. They specifically studied the Src family kinases, called SFKs. The SFKs are nonreceptor tyrosine kinases that regulate many cell processes. There are 11 types of SFKs in the human genome. Some of these SFKs are in the mitochondria and they play an essential role in the function of the mitochondria. The team found that all the TKIs they tested inhibit the kinase activity of the SKFs in the mitochondria which is responsible for the NLRP3 inflammasome.

The team's comprehensive analysis of the TKIs they tested revealed that these TKIs act as powerful agonists. In addition, the team observed off-target activity that could contribute to the side effects. "As an important finding, all TKIs we tested share a common off-target activity against the mitochondrial SFKs. Therefore, blocking the access of TKIs to mitochondria is a good way to prevent the inflammation," said Matsuzawa. They also noted that the other TKIs that do not affect the activity of the mitochondrial SFKs may overcome the inflammatory-based side effects. As another approach, when effective inhibitors of the NLRP3 inflammasome are developed, administering the TKIs at the same time as the NLRP3 inhibitors can counteract the side effects. The team's results provide insight into both the biological and the clinical significance of the NLRP3 inflammasome and the SFKs.

Looking ahead, the team's next step is to propose a new approach to avoid the inflammatory-based side effects of TKIs. They hope to lead in the development of new TKIs that do not initiate inflammation.

The research team includes Yuto Sekiguchi, Saya Takano, Takuya Noguchi, Tomohiro Kagi, Ryuto Komatsu, Maoko Tan, Yusuke Hirata, and Atsushi Matsuzawa from the Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan. Source:

Tohoku UniversityJournal reference:

Sekiguchi, Y., et al. (2023) The NLRP3 inflammasome works as a sensor for detecting hypoactivity of the mitochondrial Src family kinases. The Journal of Immunology. doi.org/10.4049/jimmunol.2200611.

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Crypto stocks down, IPOs punted amid tariff tumult

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Crypto stocks down, IPOs punted amid tariff tumult

Crypto stocks down, IPOs punted amid tariff tumult

Cryptocurrency firms felt the heat from US President Donald Trump’s sweeping tariff rollout this week as market turbulence sent share prices tumbling and foiled initial public offering (IPO) plans. 

From exchanges to Bitcoin (BTC) miners, crypto stocks suffered as much, if not more, than shares of other companies — despite the industry’s warm relationship with the US president. 

On April 2, Trump announced he was placing tariffs of at least 10% on practically all imports into the United States and adding additional “reciprocal” tariffs on some 57 countries. 

Since then, major US stock indices — including the S&P 500 and Nasdaq — tumbled by roughly 10% as traders braced for a looming trade war. 

Crypto stocks down, IPOs punted amid tariff tumult

Bitcoin miners sold off on Trump’s tariff news. Source: Morningstar

Related: Bitcoin ‘decouples,’ stocks lose $3.5T amid Trump tariff war and Fed warning of ‘higher inflation’

Sharp selloffs

Crypto exchange Coinbase — a prominent ally of Trump during the November US elections — experienced a similarly severe sell-off, with its stock price dropping by roughly 12% during the same period, according to data from Google Finance.

Bitcoin miners are also taking a hit. The CoinShares Crypto Miners ETF (WGMI) — which tracks a diverse basket of Bitcoin mining stocks — has lost roughly 13% of its value since immediately prior to Trump’s April 2 announcement, according to data from Morningstar. 

Even Strategy, one of the best-performing stocks of 2024, wasn’t immune. Its share price has fallen by around 6% on the news, Google Finance data showed.

According to Reuters, investment bank JPMorgan has raised its estimated odds of a global economic recession in 2025 to 60% from 40% previously. 

“Disruptive U.S. policies have been recognized as the biggest risk to the global outlook all year,” JP Morgan reportedly said.

“The effect … is likely to be magnified through (tariff) retaliation, a slide in U.S. business sentiment and supply-chain disruptions.”

Crypto stocks down, IPOs punted amid tariff tumult

Strategy’s shares also dropped this week. Source: Google Finance

IPO delays

The impact of US tariffs hasn’t been limited to stock price volatility. Stablecoin issuer Circle has reportedly paused plans for a 2025 IPO, citing market turbulence. 

According to The Wall Street Journal, Circle is “waiting anxiously” before taking further steps after filing to take the company public on April 1. 

It is among several companies — including fintech Klarna and ticketing service StubHub — reportedly considering altering or shelving IPO plans. 

One exception may be Bitcoin itself, which some analysts say is finally “decoupling” from the broader market.

Bitcoin’s spot price has held above $82,000 this week, even as US equities markets collapsed.

Magazine: Unstablecoins: Depegging, bank runs and other risks loom

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Politics

Brazilian court authorizes crypto seizure for debt collection — Report

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Brazilian court authorizes crypto seizure for debt collection — Report

Brazilian court authorizes crypto seizure for debt collection — Report

Brazilian judges have been authorized to seize cryptocurrency assets from debtors who owe money and are behind on their payments, signaling a growing recognition that digital assets can be both a form of payment and a store of value.

According to local media reports, the Third Panel of Brazil’s Superior Court of Justice unanimously authorized judges to send letters to cryptocurrency brokers informing them about their intent to seize an account holder’s assets to repay creditors.

The report was confirmed by the Superior Court of Justice, which issued a notice on its website.

The decision was reached unanimously by the Third Panel, which reviewed a case brought forward by a creditor.

“Although they are not legal tender, crypto assets can be used as a form of payment and as a store of value,” a translated version of the Superior Court of Justice’s memo read.

Brazilian court authorizes crypto seizure for debt collection — Report

Source: STJnoticias

Under existing rules, Brazilian judges are allowed to freeze bank accounts and order fund withdrawals, even without a debtor’s knowledge, should they rule that a creditor is owed money.

Following the recent decision, crypto assets now fall under the same purview. 

Minister Ricardo Villas Bôas Cueva, who voted in the five-person panel, said cryptocurrencies still lack formal regulation in Brazil but noted certain bills have recognized the asset class as “a digital representation of value.” 

Related: Brazil’s data watchdog upholds ban on World crypto payments

Despite regulatory uncertainty, Brazil is a major hub for crypto

Although Brazil still lacks an overarching framework for digital assets, with the country’s central bank divvying up the regulatory processes into phases, crypto adoption is surging across the country.

Brazil ranks second among all Latin American countries in terms of “crypto value received,” which is a key benchmark for adoption, according to an October report by Chainalysis. 

Brazilian court authorizes crypto seizure for debt collection — Report

In Latin America, only Argentina has higher crypto penetration in terms of value received as of June 2024. Source: Chainalysis

Earlier this year, crypto exchange Binance was granted approval to operate in the country after it acquired a São Paulo-based investment company. 

A Binance executive told Cointelegraph at the time that Brazil was making “significant strides” in regulating the industry and expects a comprehensive framework to be finalized “by mid-year.”

Nevertheless, not all of Brazil’s regulatory proposals have been favorable for the industry.

In December, the country’s central bank proposed banning stablecoin transactions on self-custodial wallets at a time when more locals were using dollar-pegged tokens to hedge against the devaluation of the Brazilian real.

Industry observers told Cointelegraph at the time that such a ban would be difficult to enforce.

“Governments can regulate centralized exchanges, but P2P transactions and decentralized platforms are much harder to control, which means the ban would likely only affect part of the ecosystem,” said Lucien Bourdon, an analyst with Trezor. 

Related: Brazilian lawmaker introduces bill to regulate Bitcoin salaries

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Environment

EcoFlow members can save up to 65% on power stations while supporting disaster relief during the 2025 Member’s Festival

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EcoFlow members can save up to 65% on power stations while supporting disaster relief during the 2025 Member's Festival

Portable power station specialist EcoFlow is kicking off its third annual Member’s Festival this month and is offering a unique new rewards program to those who become EcoFlow members. The 2025 EcoFlow Member’s Festival will offer savings of up to 65% for its participating customers, and a portion of those funds will be allocated toward rescue power solutions for communities around the globe through the company’s “Power for All” fund.

EcoFlow remains one of the industry leaders in portable power solutions and continues to trek forward in its vision to power a new tech-driven, eco-conscious future. Per its website:

Our mission from day one is to provide smart and eco-friendly energy solutions for individuals, families, and society at large. We are, were, and will continue to be a reliable and trusted energy companion for users around the world.

To achieve such goals, EcoFlow has continued to expand its portfolio of sustainable energy solutions to its community members, including portable power stations, solar generators, and mountable solar panels. While EcoFlow is doing plenty to support its growing customer base, it has expanded its reach by giving back to disaster-affected communities by helping bolster global disaster response efforts the best way it knows how– with portable power solutions.

EcoFlow Member
Source: EcoFlow

EcoFlow and its members look to provide “Power for All”

Since 2023, EcoFlow has collaborated with organizations worldwide as part of its “Power for All” mission. This initiative aims to ensure access to reliable and timely power to disaster-affected communities across the globe, including rescue agencies, affected hospitals, and shelters, to support rescue and recovery efforts.

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This fund most recently provided aid for communities affected by the recent Los Angeles wildfires, assistance to the Special Forces Charitable Trust (SFCT) in North Carolina following severe hurricanes, and support for non-profits engaged in hurricane preparedness in Florida and the Gulf Coast. Per Jodi Burns, CEO of the Special Forces Charitable Trust:

In the wake of devastating storms in Western North Carolina, reliable power was a critical need for the families we serve. Thanks to EcoFlow’s generous donation of generators, we were able to provide immediate relief, ensuring these families and their communities had access to power when they needed it most. We are so impressed with EcoFlow’s commitment to disaster response through their ‘Power for All’ program. It has made a tangible impact, and we are deeply grateful for their support and partnership in helping these families recover and rebuild.

In 2024, the US experienced 27 weather and climate events, each causing losses exceeding $1 billion, marking the second-highest annual total on record, according to National Centers for Environmental Information. The increasing frequency and severity of natural disasters underscore the critical need for reliable and timely power solutions during emergencies, much like EcoFlow and its members are helping provide through the “Power For All” initiative.

To support new and existing EcoFlow members, the company is celebrating its third annual Member’s Festival throughout April to offer a do-not-miss discount on its products and donate a portion of all sales to the “Power for All” fund to provide rescue power to those in need in the future. Learn how it all works below.

Source: EcoFlow

Save big and give back during the 2025 Member’s Festival

As of April 1st, you can now sign up to become an EcoFlow member to participate in the company’s exclusive 2025 Member Festival.

As a member, you can earn “EcoFlow Power Points” by completing tasks like registration, referrals, and product purchases and tracking your individual efforts toward disaster preparedness and recovery.

Beginning April 4, EcoFlow members will also be able to take advantage of exclusive discounts of up to 65% off select portable power stations, including the DELTA Pro Ultra, DELTA Pro 3, DELTA 2 Max, DELTA 3 Plus, RIVER 3 Plus, and more. However, these sale prices only last through April 25, so you’ll want to move quickly!

Click here to learn more about EcoFlow’s “Power for All” campaign. To register for EcoFlow’s 2025 Member Festival in the US, visit the EcoFlow website. To register as a member in Canada, visit here.

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