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America's Heartland Free Speech Links from other news sources. Trump

Yesterday’s historic event. 250 years of greatness.

Yesterday’s historic event. 250 years of greatness.

Our country had several historic events yesterday. The army’s 250th., President Trumps, Birthday, and the Vice Presidents Wedding Anniversary.

Trump hailed the U.S. Army as the “fiercest and bravest fighting force ever to stride the face of the earth” and commended soldiers who have fought and died for the country in patriotic-themed remarks after the parade concluded.

Our best.

The line to get into the parade extends multiple city blocks, stretching around the Smithsonian Museum of American History, and then looping back into the street.

And yes, the hate groups were out also.

Hate group also shows up.

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Commentary Democrat Insurrection Links from other news sources.

Where’s the Rogue Cop? Insurrectionists storm the Capitol.

Where’s the Rogue Cop? Insurrectionists storm the Capitol.

We have this from CNN.

A group of approximately 75 protesters were demonstrating at the Supreme Court, just across the street from the US Capitol, according to a statement from the Capitol Police. As the group was leaving the area, officers began establishing a perimeter of bike racks to keep the protesters away from the Capitol.

“A few people pushed the bike rack down and illegally crossed the police line while running towards the Rotunda Steps,” the Capitol Police said. “Our officers immediately blocked the group and began making arrests.”

Police said, “All will be charged with unlawful demonstration and crossing a police line. Additional charges for some will include assault on a police officer and resisting arrest.”

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Commentary Israel Links from other news sources. Opinion Terrorism Uncategorized

Iran fires back. Launches over 100 drones in 1st response to attack. IAF downs them

Iran fires back. Launches over 100 drones in 1st response to attack. IAF downs them.

If you went to bed early, Israel did a first strike on Iran’s Nuclear sites, Military leaders, Scientists, and hopefully the so-called religious leaders. There were suspicions that Iran was planning attacks on Israel. And sure enough, it happened.

Israel alerted its citizens on Friday morning that Iran had launched more than 100 drones — which would take several hours to arrive — telling people nationwide to remain near bomb shelters.

Three hours later, the IDF Home Front Command lifted its instruction to Israelis to remain near shelters without a single siren sounding in the country, after it worked to shoot them down outside Israeli territory.

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Elections Links from other news sources. The Courts Trump

I love winning. Democrat challenge to Trump suffers major blow.

I love winning. Democrat challenge to Trump suffers major blow.

Another court case and another win. U.S. District Judge Amir Ali dismissed a lawsuit from the Democratic National Committee targeting a number of Trump’s many executive orders Tuesday.

Specifically, this DNC lawsuit claimed that some of Trump’s executive orders would erode the Federal Election Commission’s independence. The FEC had pledged to remain independent, had received no directive from the White House to change its practices and vowed to abide by the law. Without evidence undermining those promises, Ali said he was compelled to dismiss the suit.

Given those assurances, Ali said, the Democratic committees needed to “point to a concrete basis for [the] conclusion” that the FEC’s independence had been undermined or facing a looming threat of such interference.

“They have not done so here,” he concluded.

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Links from other news sources. Medicine Reprints from others. Science

You make the call. Ivermectin and Cancer research.

You make the call. Ivermectin and Cancer research.

Ivermectin, a potential anticancer drug derived from an antiparasitic drug. You may have heard that there are ongoing studies of Ivermectin being used as a treatment for different types of cancer. Some using it alone, some using it with other drugs. Here is what the NIH has on this. Of course, when Collins and Tony the Fauch were running the NIH, THIS WOULD NOT HAVE BEEN WIDLY PUBLISIZED.

The role of IVM in different cancers
2.1. Breast cancer
Breast cancer is a malignant tumor produced by gene mutation in breast epithelial cells caused by multiple carcinogens. The incidence of breast cancer has increased each year, and it has become one of the female malignant tumors with the highest incidence in globally. On average, a new case is diagnosed every 18 seconds worldwide [30,31]. After treatment with IVM, the proliferation of multiple breast cancer cell lines including MCF-7, MDA-MB-231 and MCF-10 was significantly reduced. The mechanism involved the inhibition by IVM of the Akt/mTOR pathway to induce autophagy and p-21-activated kinase 1(PAK1)was the target of IVM for breast cancer [32]. Furthermore, Diao’s study showed that IVM could inhibit the proliferation of the canine breast tumor cell lines CMT7364 and CIPp by blocking the cell cycle without increasing apoptosis, and the mechanism of IVM may be related to the inhibition of the Wnt pathway [33].

Triple-negative breast cancer (TNBC) refers to cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2(HER2) and is the most aggressive subtype of breast cancer with the worst prognosis. In addition, there is also no clinically applicable therapeutic drug currently [34,35]. A drug screening study of TNBC showed that IVM could be used as a SIN3-interaction domain (SID) mimic to selectively block the interaction between SID and paired a-helix2. In addition, IVM regulated the expression of the epithelial mesenchymal-transition (EMT) related gene E-cadherin to restore the sensitivity of TNBC cells to tamoxifen, which implies the possibility that IVM functions as an epigenetic regulator in the treatment of cancer[36].

Recent studies have also found that IVM could promote the death of tumor cells by regulating the tumor microenvironment in breast cancer. Under the stimulation of a tumor microenvironment with a high level of adenosine triphosphate (ATP) outside tumor cells, IVM could enhance the P2 × 4/ P2 × 7/Pannexin-1 mediated release of high mobility group box-1 protein (HMGB1) [37]. However, the release of a large amount of HMGB1 into the extracellular environment will promote immune cell-mediated immunogenic death and inflammatory reactions, which will have an inhibitory effect on the growth of tumor cells. Therefore, we believe that the anticancer effect of IVM is not limited to cytotoxicity, but also involves the regulation of the tumor microenvironment. IVM regulates the tumor microenvironment and mediates immunogenic cell death, which may be a new direction for research exploring anticancer mechanisms in the future.

2.2. Digestive system cancer
Gastric cancer is one of the most common malignant tumors worldwide. In the past year, more than one million patients with gastric cancer have been diagnosed worldwide [38]. Nambara’s study showed that IVM could significantly inhibit the proliferation of gastric cancer cells in vivo and in vitro and that the inhibitory effect of IVM depended on the expression of Yes-associated protein 1(YAP1)[39]. The gastric cancer cell lines MKN1 and SH-10-TC have higher YAP1 expression than MKN7 and MKN28 cells, so MKN1 and SH-10-TC cells are sensitive to IVM, while MKN7 and MKN28 are not sensitive to IVM.YAP1 plays an oncogenic role in tumorigenesis, indicating the possibility of the use of IVM as a YAP1 inhibitor for cancer treatment [40].

In a study that screened Wnt pathway inhibitors, IVM inhibited the proliferation of multiple cancers, including the colorectal cancer cell lines CC14, CC36, DLD1, and Ls174 T, and promoted apoptosis by blocking the Wnt pathway [41]. After intervention with IVM, the expression of caspase-3 in DLD1 and Ls174 T cells increased, indicating that IVM has an apoptosis-inducing effect and inhibits the expression of the downstream genes AXIN2, LGR5, and ASCL2 in the Wnt/β-catenin pathway. However, the exact molecular target of IVM that affects the Wnt/β-catenin pathway remains to be explored.

Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. Approximately 80% of cases of liver cancer are caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infection [42]. IVM could inhibit the development of hepatocellular carcinoma by blocking YAP1 activity in spontaneous liver cancer Mob1b-/- mice [43].Cholangiocarcinoma is a malignant tumor that originates in the bile duct inside and outside the liver. Intuyod’s experiment found that IVM inhibited the proliferation of KKU214 cholangiocarcinoma cells in a dose- and time-dependent manner [44]. IVM halted the cell cycle in S phase and promoted apoptosis. Surprisingly, gemcitabine-resistant KKU214 cells showed high sensitivity to IVM, which suggested that IVM shows potential for the treatment of tumors that are resistant to conventional chemotherapy drugs.

2.3. Urinary system cancer
Renal cell carcinoma is a fatal malignant tumor of the urinary system derived from renal tubular epithelial cells. Its morbidity has increased by an average of 2% annually worldwide and the clinical treatment effect is not satisfactory [[45], [46], [47]]. Experiments confirmed that IVM could significantly inhibit the proliferation of five renal cell carcinoma cell lines without affecting the proliferation of normal kidney cells, and its mechanism may be related to the induction of mitochondrial dysfunction [48]. IVM could significantly reduce the mitochondrial membrane potential and inhibit mitochondrial respiration and ATP production. The presence of the mitochondrial fuel acetyl-L-carnitine (ALCAR), and the antioxidant N-acetyl-L-cysteine (NAC), could reverse IVM-induced inhibition. In animal experiments, the immunohistochemical results for IVM-treated tumor tissues showed that the expression of the mitochondrial stress marker HEL was significantly increased, and the results were consistent with those of the cell experiments.

Prostate cancer is a malignant tumor derived from prostate epithelial cells, and its morbidity is second only to that of lung cancer among men in Western countries [49]. In Nappi’s experiment, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel [50]. Interestingly, IVM also restored the sensitivity of the triple-negative breast cancer to the anti-estrogen drug tamoxifen [36], which also implies the potential for IVM to be used in endocrine therapy. Moreover, IVM was also found to have a good inhibitory effect on the prostate cancer cell line DU145 [51].

2.4. Hematological cancer
Leukemia is a type of malignant clonal disease caused by abnormal hematopoietic stem cells [52]. In an experiment designed to screen potential drugs for the treatment of leukemia, IVM preferentially killed leukemia cells at low concentrations without affecting normal hematopoietic cells [51]. The mechanism was related to the increase in the influx of chloride ions into the cell by IVM, resulting in hyperpolarization of the plasma membrane and induction of reactive oxygen species (ROS) production. It was also proven that IVM has a synergistic effect with cytarabine and daunorubicin on the treatment of leukemia. Wang’s experiment found that IVM could selectively induce mitochondrial dysfunction and oxidative stress, causing chronic myeloid leukemia K562 cells to undergo increased caspase-dependent apoptosis compared with normal bone marrow cells [53]. It was also confirmed that IVM inhibited tumor growth in a dose-dependent manner, and dasatinib had improved efficacy.

2.5. Reproductive system cancer
Cervical cancer is one of the most common gynecological malignancies, resulting in approximately 530,000 new cases and 270,000 deaths worldwide each year. The majority of cervical cancers are caused by human papillomavirus (HPV) infection [54,55]. IVM has been proven to significantly inhibit the proliferation and migration of HeLa cells and promote apoptosis [56]. After intervention with IVM, the cell cycle of HeLa cells was blocked at the G1/S phase, and the cells showed typical morphological changes related to apoptosis.

Ovarian cancer is a malignant cancer that lacks early clinical symptoms and has a poor therapeutic response. The 5-year survival rate after diagnosis is approximately 47% [27,57]. In a study by Hashimoto, it found that IVM inhibited the proliferation of various ovarian cancer cell lines, and the mechanism was related to the inhibition of PAK1 kinase [58]. In research to screen potential targets for the treatment of ovarian cancer through the use of an shRNA library and a CRISPR/Cas9 library, the oncogene KPNB1 was detected. IVM could block the cell cycle and induce cell apoptosis through a KPNB1-dependent mechanism in ovarian cancer [59]. Interestingly, IVM and paclitaxel have a synergistic effect on ovarian cancer, and combined treatment in in vivo experiments almost completely inhibited tumor growth. Furthermore, according to a report by Zhang, IVM can enhance the efficacy of cisplatin to improve the treatment of epithelial ovarian cancer, and the mechanism is related to the inhibition of the Akt/mTOR pathway [60].

2.6. Brain glioma
Glioma is the most common cerebral tumor and approximately 100,000 people worldwide are diagnosed with glioma every year. Glioblastoma is the deadliest glioma, with a median survival time of only 14-17 months [61,62]. Experiments showed that IVM inhibited the proliferation of human glioblastoma U87 and T98 G cells in a dose-dependent manner and induced apoptosis in a caspase-dependent manner [63]. This was related to the induction of mitochondrial dysfunction and oxidative stress. Moreover, IVM could induce apoptosis of human brain microvascular endothelial cells and significantly inhibit angiogenesis. These results showed that IVM had the potential to resist tumor angiogenesis and tumor metastasis. In another study, IVM inhibited the proliferation of U251 and C6 glioma cells by inhibiting the Akt/mTOR pathway [64].

In gliomas, miR-21 can regulate the Ras/MAPK signaling pathway and enhance its effects on proliferation and invasion [65]. The DDX23 helicase activity affects the expression of miR-12 [66]. IVM could inhibit the DDX23/miR-12 signaling pathway by affecting the activity of DDX23 helicase, thereby inhibiting malignant biological behaviors. This indicated that IVM may be a potential RNA helicase inhibitor and a new agent for of tumor treatment. However, here, we must emphasize that because IVM cannot effectively pass the blood-brain barrier [67], the prospect of the use of IVM in the treatment of gliomas is not optimistic.

2.7. Respiratory system cancer
Nasopharyngeal carcinoma is a malignant tumor derived from epithelial cells of the nasopharyngeal mucosa. The incidence is obviously regional and familial, and Epstein-Barr virus (EBV) infection is closely related [68]. In a study that screened drugs for the treatment of nasopharyngeal cancer, IVM significantly inhibited the development of nasopharyngeal carcinoma in nude mice at doses that were not toxic to normal thymocytes [69]. In addition, IVM also had a cytotoxic effect on a variety of nasopharyngeal cancer cells in vitro, and the mechanism is related to the reduction of PAK1 kinase activity to inhibit the MAPK pathway.

Lung cancer has the highest morbidity and mortality among cancers [70]. Nishio found that IVM could significantly inhibit the proliferation of H1299 lung cancer cells by inhibiting YAP1 activity [43]. Nappi’s experiment also proved that IVM combined with erlotinib to achieved a synergistic killing effect by regulating EGFR activity and in HCC827 lung cancer cells [50]. In addition, IVM could reduce the metastasis of lung cancer cells by inhibiting EMT.

2.8. Melanoma
Melanoma is the most common malignant skin tumor with a high mortality rate. Drugs targeting BRAF mutations such as vemurafenib, dabrafenib and PD-1 monoclonal antibodies, including pembrolizumab and nivolumab have greatly improved the prognosis of melanoma [71,72]. Gallardo treated melanoma cells with IVM and found that it could effectively inhibit melanoma activity [73]. Interestingly, IVM could also show activity against BRAF wild-type melanoma cells, and its combination with dapafinib could significantly increase antitumor activity. Additionally, it has been confirmed that PAK1 is the key target of IVM that mediates its anti-melanoma activity, and IVM can also significantly reduce the lung metastasis of melanoma in animal experiments. Deng found that IVM could activate the nuclear translocation of TFE3 and induce autophagy-dependent cell death by dephosphorylation of TFE3 (Ser321) in SK-MEL-28 melanoma cells [74]. However, NAC reversed the effect of IVM, which indicated that IVM increased TFE3-dependent autophagy through the ROS signaling pathway.

3. IVM-induced programmed cell death in tumor cells and related mechanisms
3.1. Apoptosis
IVM induces different programmed cell death patterns in different tumor cells (Table 1). As shown in Table 1, the main form of IVM induced programmed cell death is apoptosis. Apoptosis is a programmed cell death that is regulated by genes to maintain cell stability. It can be triggered by two activation pathways: the endogenous endoplasmic reticulum stress/mitochondrial pathway and the exogenous death receptor pathway [75,76]. The decrease in the mitochondrial membrane potential and the cytochrome c is released from mitochondria into the cytoplasm was detected after the intervention of IVM in Hela cells [56].Therefore, we infer that IVM induces apoptosis mainly through the mitochondrial pathway. In addition, morphological changed caused by apoptosis, including chromatin condensation, nuclear fragmentation, DNA fragmentation and apoptotic body formation were observed. Finally, IVM changed the balance between apoptosis-related proteins by upregulating the protein Bax and downregulating anti-apoptotic protein Bcl-2, thereby activating caspase-9/-3 to induce apoptosis [48,53,63] (Fig. 2 ).

Summary and outlooks.

Malignant tumors are one of the most serious diseases that threaten human health and social development today, and chemotherapy is one of the most important methods for the treatment of malignant tumors. In recent years, many new chemotherapeutic drugs have entered the clinic, but tumor cells are prone to drug resistance and obvious adverse reactions to these drugs. Therefore, the development of new drugs that can overcome resistance, improve anticancer activity, and reduce side effects is an urgent problem to be solved in chemotherapy. Drug repositioning is a shortcut to accelerate the development of anticancer drugs.

As mentioned above, the broad-spectrum antiparasitic drug IVM, which is widely used in the field of parasitic control, has many advantages that suggest that it is worth developing as a potential new anticancer drug. IVM selectively inhibits the proliferation of tumors at a dose that is not toxic to normal cells and can reverse the MDR of tumors. Importantly, IVM is an established drug used for the treatment of parasitic diseases such as river blindness and elephantiasis. It has been widely used in humans for many years, and its various pharmacological properties, including long- and short-term toxicological effects and drug metabolism characteristics are very clear. In healthy volunteers, the dose was increased to 2 mg/Kg, and no serious adverse reactions were found, while tests in animals such as mice, rats, and rabbits found that the median lethal dose (LD50) of IVM was 10-50 mg/Kg [112] In addition, IVM has also been proven to show good permeability in tumor tissues [50]. Unfortunately, there have been no reports of clinical trials of IVM as an anticancer drug. There are still some problems that need to be studied and resolved before IVM is used in the clinic.

(1) Although a large number of research results indicate that IVM affects multiple signaling pathways in tumor cells and inhibits proliferation, IVM may cause antitumor activity in tumor cells through specific targets. However, to date, no exact target for IVM action has been found. (2) IVM regulates the tumor microenvironment, inhibits the activity of tumor stem cells and reduces tumor angiogenesis and tumor metastasis. However, there is no systematic and clear conclusion regarding the related molecular mechanism. Therefore, in future research, it is necessary to continue to explore the specific mechanism of IVM involved in regulating the tumor microenvironment, angiogenesis and EMT. (3) It has become increasingly clear that IVM can induce a mixed cell death mode involving apoptosis, autophagy and pyroptosis depending on the cell conditions and cancer type. Identifying the predominant or most important contributor to cell death in each cancer type and environment will be crucial in determining the effectiveness of IVM-based treatments. (4) IVM can enhance the sensitivity of chemotherapeutic drugs and reduce the production of resistance. Therefore, IVM should be used in combination with other drugs to achieve the best effect, while the specific medication plan used to combine IVM with other drugs remains to be explored.

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California. Commentary Democrat Illegals Leftist Virtue(!) Links from other news sources. Riots

Define what constitutes unlawful. Something like I know it when I see it.

Define what constitutes unlawful. Something like I know it when I see it.

The past couple days the leftists have been rioting in LA because ICE has come to town to clean out a den of hard-core criminals. For some reason they think that attacking federal agents is the right thing to do. Take a look at the videos and statements below. You be the judge.

Officials from the Service Employees International Union said in a statement that its California president, David Huerta, was detained and injured during a downtown raid “while exercising his First Amendment right to observe and document law enforcement activity.” What they leave out is that he stood in front of and blocked a vehicle leaving. A vehicle carrying criminals.

The insurrectionists hurl an Unregistered Destructive Device into the federal facility then run from resulting salvos. pic.twitter.com/Phuoh7obkK

— Alan Bings (@AlanBings) June 8, 2025

Rioters are trying to light buildings on fire in Compton.

JUST IN : A new fire has just been started as protestors continue to clash with police.

Compton, CA pic.twitter.com/dOSF1qQyOx

— Anthony (@AnthonyCabassa_) June 8, 2025

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Commentary Food Links from other news sources.

Roaches, rats and slime. See worst Sacramento County restaurant inspections. Where Progressive Supremacists eat.

Roaches, rats and slime. See worst Sacramento County restaurant inspections. Where Progressive Supremacists eat.

Recently a lurker who just can’t stay away commented on a health inspection of a location in New Jersey. A location that this person would never be able to visit. For some reason this person ignores their own back yard. So, I thought maybe I should take a look.

Sacramento County inspectors shut down three local restaurants, two gas stations and a Moose lodge in May due to a variety of food safety violations. Reasons for the closures ranged from cockroaches, live rats and rodent droppings to mold, slime and clogged drains.

Read more at: https://www.sacbee.com/news/local/article307796465.html#storylink=cpy

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Commentary Democrat How funny is this? Links from other news sources. Polls

CNN’S surprised. I’m not. Just 16% Say Dems Have ‘Strong Leaders’.

CNN’S surprised. I’m not. Just 16% Say Dems Have ‘Strong Leaders’.

How telling is that? Americans no longer have faith in a party that promotes DEI and affirmative action politicians. So among Democrats and Democratic leaners, 32% say Democrats are the party with strong leaders. I mean, of their own kind.

82% of Republican or Republican leaders say that about the GOP. Only 41% of Democrats say they’re the party that gets things done of their own kind.

CNN POLL CONDUCTED BY SSRS
May 5-26
Which Party Is:
Party With Strong Leaders?

Republicans 40%
Democrats 16%
Neither 43%

Amid a wave of skepticism among Democrats about their own party’s effectiveness, the GOP currently holds the advantage across several key attributes

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Black Supremacy Commentary Corruption Crime Leftist Virtue(!) Links from other news sources. Medicade Undocumented

Nevada DHHS Specialist Caught on Camera Admitting to “Bending the Rules” to Provide Benefits for the Undocumented.

Nevada DHHS Specialist Caught on Camera Admitting to “Bending the Rules” to Provide Benefits for the Undocumented.

Recently a state employee in Nevada was caught on camera bragging about getting benefits that were not allowed for illegals.

When confronted with a video of his comments, Deshaun Mack said, “I say a lot of things that I don’t mean” and eventually admitted, “I lie all the time.” He suggested he may have exaggerated to impress the undercover journalist, saying, “Absolutely,” when asked if that was the reason for his comments. Despite the specificity of his original statements, Mack ultimately claimed, “None of those words I said were true.”

And the Governors response?

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Elections Links from other news sources. MSM

CBS has no say so. Paramount trying to end the attack on Trump.

CBS has no say so. Paramount trying to end the attack on Trump.

The past six months or so, folks at CBS forgot that they don’t get to slander folks without consequences. Trump filed a lawsuit and Paramount cried uncle.

The lawsuit stems from CBS’ “60 Minutes” interview with Kamala Harris last fall, which the president claims were deceitfully edited. Trump is asking for $25 million to settle and an apology from the news network, WSJ reports.

CBS cried foul and Paramount quietly got rid of several folks. OK they resigned. I guess they didn’t want to be fired. Winning.

The post Trump Shuts Down Paramount’s $15 Million Offer to Settle ’60 Minutes’ Lawsuit | Report appeared first on The Wrap.