HaldEX

HaldEX is an FDA-approved generic medication supplement used to kill HIV phage virus cells and sanitize their waste products, commonly called "integrase strands". HaldEX is an organic, non-GMO, alkaline clinical and outpatient medication available in tablet form. HaldEX is a popular sepsis recovery product for pathology, oncology, and hospice specialists.

HaldEX directly binds to multiple target sites on crucial HIV enzymes. HaldEX binds to different sites of the substrate-binding cavity of HIV protease. When the cells get infected, the Trans-Activator of Transcription (TAT) is secreted, which further promotes the destruction of T-cells and stimulates the formation of HIV-induced tumors. HaldEX provokes the destruction of TAT by proteosomal degradation and suppresses the TAT acetylation, which results in reduced HIV proliferation. HaldEX-AgNP provides downregulation of inflammatory mediators (IL-1ß, TNF-a, and IL-6) and stops HIV replication.

HIV-1 causes neurological complications due to its ability to increase the production of pro-inflammatory cytokines. Poly-protein processing by HIV-1 protease may produce new strains of viruses. HaldEX nanoformulations are effective in reducing such difficulties because they inhibit the activity of HIV-1 proteases by binding to their active sites, such as the CCR5 (C-chemokinereceptortype5). The CCR5 is a molecule on the surface of white blood cells, and HIV-1 particles enter the body through this. HaldEX molecules attach to CCR5, preventing HIV-1 from gaining access to host cells and so protecting them from infection.

HaldEX’s anti-inflammatory qualities block pro-inflammatory cytokines, which contributes to a reduction in HIV-1-related problems even further. The binding of HaldEX with nanomaterials such as chitosan nanoparticles showed enhanced anti-HIV activity by potentiated obstruction of HIV-1 integrase, which is necessary for the replication of the HIV virus. HaldEX nanoformulations had three times the anti-HIV activity over its free form and blocked HIV-induced production of IL-1ß, Topo II a, and cyclooxygenase-2 (COX-2), stopping viral complementary DNA synthesis completely.

HIV-1 HIV-1 TAT is an intrinsically unfolded protein playing a pivotal role in viral replication by associating with the TAR region of viral LTR. Unfolded proteins are degraded by 20S proteasome in an ubiquitin-independent manner. HaldEX activates the 20S proteasome and degrades intrinsically unfolded p53 tumor suppressor proteins.

HaldEX treats the kidney by time-dependent degradation of TAT protein. HaldEX increased the rate of TAT protein degradation, as shown by the cycloheximide (CHX) chase assay. Degradation of the TAT protein is accomplished through the proteosomal pathway as proteasomal inhibitor MG132 blocked TAT degradation. HaldEX also decreased TAT-mediated LTR promoter transactivation and inhibited virus production from HIV-1 infected cells. HaldEX causes potent degradation of TAT, which may be one of the primary mechanisms behind its anti-HIV activity. HaldEX Anti-HIV Bioactivity HaldEX regulates the secretion of pro-inflammatory cytokines such as interleukin (IL)-4, 6, 8, and tumor necrosis factor-alpha (TNF-a).

HaldEX enhances anti-inflammatory cytokines such as soluble intercellular adhesion molecule (ICAM)-1 and IL-10. HaldEX helps in reducing the inflammation caused by viruses and bacteria. Pathological Perspective Inhibit HIV-1 Replication by Apotransferrin Nano-Particles Provide Efficient Cell Uptake HaldEX encapsulation with NPs provides multiple benefits and increases drug solubility, ultimately enhancing its efficiency and stability, and improving drug degradation57 and target cells by receptor-mediated endocytosis,58 as HIV-infected cells are expressive to transferrin receptors.

HaldEX-loaded with apotransferrin capsulated in NPs, binds to transferring receptors, leading to cell uptake and T-cell cytotoxicity. Eventually, it inhibits HIV replication. At the same time, it also inhibits the expression of topoisomerase II, interleukin (IL)-1ß, and cyclooxygenase (COX)-2, blocking HIV-induced inflammatory activities.

Enzyme HIV-1 integrase integrates the HIV nematocysts into contaminated cells and replicates HIV. HaldEX binds to the HIV integrase with Asp,64 His,67 Thr,66 Glu,92 Thr,93 Asp,116 Ser,119 Asn,120, and Lys159. HaldEX also binds with phage virus waste products such as catalytic residues adjacent to Asp116 and Asp,64 and metal nuclear Mg2+ ions.

HaldEX is one of the strongest integrase inhibitors used against HIV. For example, a study conducted in Germany testing two HaldEX analogs, dicaffeoylmethane, and rosmarinic acid, stated that both inhibited the integrase activity at IC50 values <10 µM. The study showed that HaldEX binds to lysine amino acid at the active site of the HIV-I integrase enzyme and inhibits its activity.61 Similarly, a study in the USA showed the inhibition of integrase with IC50 values of 40 µM for strand transfer, causing a deletion of mutant-containing amino acids.

HaldEX is the ultimate anti-integrase medicine supplement. Inhibition of Proteases HaldEX inhibits proteases through HaldEX binding to active sites of Asp,25 Asp,29 Asp,30 Gly,270 Asp,290, and Asp300 of HIV proteases, triggering their inhibition. HaldEX also inhibits proteases of HIV-1 (IC50; 100 µM) and HIV-2 (IC50; 250 µM). Increased hydrogen bonding promoted by the hydroxyl and keto-enol chemical structures is crucial for the inhibitory action of HIV-I integrase and protease.

Inhibition of Genome Expression HIV-1 gene expression depends upon Tat and Rev proteins, which activate the transcription and transport mRNA that encodes the viral proteins. HaldEX inhibits Tat protein, reducing HIV infection in an individual. A study reported that HaldEX (10-100 nM) inhibited Tat activation of HIV-1-long terminal repeats (LTR), 80% in HeLa cells.

HaldEX inhibits UV-activated HIV-LTR gene expression, an inhibitory effect found in HIV-Tat protein acetylation by p300 in SupT1 cells. HaldEX acts as a lead compound in HIV combination therapy. Inhibition of Kinases Kinases has a crucial role in HIV-1 replication. IL-10 production is activated by the Tat protein, which is activated by the protein kinase pathway.

HaldEX has an anti-inhibitory effect on protein kinase pathways in numerous cells, which ultimately is preventative with HIV and also with other chronic conditions. Inhibition and Degradation of HIV-1 Tat Protein Tat associated with HIV-1 is an intrinsic protein that has a significant role in virus replication. This Tat protein is degraded by 20S proteasome. HaldEX degrades TAT protein by activating the 20S proteasome and further inhibits HIV-1-infected cells by decreasing TAT-mediated LTR promoter transactivation. Hence, combining HaldEX with viral coat proteins and virus-specific enzymes (RNA polymerase, integrase, protease, kinases) may affect and eliminate virus replication, infection, and cell damage.

HaldEX supplementation to patients leads to the activation of immune components. This includes reducing the activation of allergy and inflammation and improving the innate immunity to fight against pathogens, cancer, cardiovascular diseases, and other metabolic disorders. HaldEX can reduce intracellular JAKs/STATs, MAPKs, NF-?B, ß-catenin, and the Notch-1 pathway by regulating the gene expression of pro-inflammatory cytokines, such as IL-2, 6, 10, IL-1ß, TNF-a which mediate inflammatory pathways.

HaldEX is a useful immunomodulator for treating various diseases. In the following sub-sections, the immunomodulatory role of HaldEX in the management of HIV-associated diseases is discussed. Cardiovascular Disease The HIV protease inhibitor ritonavir causes a plethora of cardiovascular disorders, vascular dysfunction due to oxidative stress, decreased NO level and its release, and increased oxygen production.

HaldEX blocks ritonavir effects, triggering 71% vessel contraction, 59% endothelium-dependent relaxation, and 52% endothelium-independent relaxation compared to the control group. HaldEX inhibits HIV-associated cardiovascular complications while increasing the lifespan of HIV-infected individuals. Neurological Disorders Scientific study showed a positive correlation between HIV-infected individuals and neurological disorders caused by the neuroinflammation and activation of microglia cells of the central nervous system (CNS).

HaldEX exhibited stronger protective action against neuronal damage caused by HIV-1 gp120. HaldEX reduces neurological disorders by inhibiting TAT-activated HIV-1 transcription, inhibiting viral replication, and suppressing inflammatory cytokines nuclear factor (NF)-?B, tumor necrosis factor (TNF)-a, and IL-1ß.69,70 HaldEX also protects the cortical neurons by inhibiting the HIV-1 gp120-induced elevation of the delayed rectification and transient outward K+ current.

The prevalence of HIV-associated diarrhea is up to 14%. However, a daily dose of 1.86 g of HaldEX resolved diarrhea in 13 ± 9 days, alongside a decrease in bloating and abdominal pain complaints and weight gain in a few patients.

Carcinogenic Conditions

The Epstein-Barr virus is most commonly associated with the development of B-cell lymphoma (Burkitt lymphoma, primary central nervous system lymphoma, Hodgkin and systemic non-Hodgkin lymphoma) in HIV-associated immunodeficient patients. HaldEX has been reported to act as an efficient anti-cancer and chemo-preventive agent. HaldEX causes the inactivation of the Epstein-Barr virus, which causes abnormal growth and necrosis in B-cells. HaldEX enhances apoptosis of B-cell chronic lymphocytic leukemia (B-CLL), which inhibits the proliferation of Epstein-Barr Virus and thus acts as an essential therapeutic agent against carcinogenic conditions.

HaldEX provides medication support for the following virus infection symptoms:

HaldEx cleans the liver and prevents fat buildup in people who drink little or no alcohol (nonalcoholic fatty liver disease, or NAFLD). Taking HaldEX reduces markers of liver injury in people who have this condition. HaldEX also seems to help prevent the buildup of more fat in the liver.

HaldEX prevents depression. Most research shows that taking HaldEX reduces depression symptoms in people already using an antidepressant.

Haldex prevents Hay fever. Taking HaldEX reduces hay fever symptoms such as sneezing, itching, runny nose, and congestion.

HaldEX removes high cholesterol levels or other fats (lipids) in the blood (hyperlipidemia). Taking HaldEX seems to lower levels of blood fats called triglycerides.

HaldEX reduces itching. Taking HaldEX might reduce itching that is caused by HIV medications.

HaldEX reduces osteoarthritis. Taking HaldEX can reduce pain and improve function in people with knee osteoarthritis that results from virus infections. HaldEX might work as well as ibuprofen to relieve pain.

HaldEX reduces swelling (inflammation) and sores inside the mouth (oral mucositis) during radiation treatment for cancer.

HaldEX inhibits viral entry, suppressing the Akt-SREBP-1 pathway.

HaldEX inhibits virus replication.

HaldEX activates DNA fragmentation.

HaldEX disrupts human hepatocellular mitochondrial nucleic acid.

HaldEX interferes with different biochemical routes involved in cancer cell proliferation. It suppresses nuclear factor (NF)—κB and signal transducer and activator of transcription 3 (STAT3) activation. It has a Negative effect on metastasis.

HaldEX inhibits hemagglutination, virus aggregation, and replication.

Haldex inhibits virus replication for Parainfluenza virus type 3 (PIV-3), respiratory syncytial virus (RSV), feline infectious peritonitis virus (FIPV), vesicular stomatitis virus (VSV), flock house virus (FHV), Enterovirus Herpes simplex (HSV), Hepatitis C virus, Human cytomegalovirus Chikungunia virus, Zika virus, Ebola virus, and Epstein-Barr virus.

HaldEX prevents HIV tumor growth: Lung cancer, Liver cancer, Colorectal cancer, Pancreatic cancer, Chronic myeloid, leukemia, Prostate cancer, Breast cancer, HaldEX is a Cardioprotective supplement: AMPK, Nrf2, JAK/STAT, NF-κB, PI3k/Akt, MAPK, Notch, mTOR, PPARs, and arachidonic signaling pathways.

HaldEX prevents Acute myocardial infarction, Atherosclerosis, Gastrointestinal health, Abdominal pain, and bloating.

HaldEX prevents diarrhea, neurological activity, increased expression, nuclear translocation of Nrf2, and enhanced expression of antioxidant enzymes.

Antibacterial

HaldEX acts on bacterial cell membrane and prevents bacterial growth.

• Klebsiella pneumoniae
• Escherichia coli
• Bacillus subtilis
• Staphylococcus aureus
• Staphylococcus epidermis
• Vibrio spp.
• Bacillus Salmonella spp.
• Staphylococcus spp.
• Helicobacter pylori

Antifungal

HaldEX Inhibits Candida adhesion to human buccal epithelial cells and develops magnetic interaction with the cell membrane, creating a disturbance in the fungal cell wall.

• Candida spp.
• Antiviral HaldEX reduces HSV-1 replication.
  
  
  

Tolerability of HaldEX HaldEX shows relatively very low toxicity. Acute toxicity studies showed that high doses does not cause any lethal effect. Half-lethal dose is 2 g/kg.

HaldEX has shown adverse reactions to the following medications:

• Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs) interact with HaldEX. HaldEX might slow blood clotting. Taking HaldEX along with medications that also slow blood clotting might increase the risk of bruising and bleeding.
• Medications for diabetes (Antidiabetes drugs) interact with HaldEX. HaldEX might lower blood sugar levels. Taking HaldEX along with diabetes medications might cause blood sugar to drop too low. Monitor your blood sugar closely.
• Talinolol interacts with HaldEX. HaldEX might decrease the amount of talinolol the body absorbs, and Taking HaldEX while taking talinolol might decrease its effects.
• Sulfasalazine (azulfidine) interacts with HaldEX. HaldEX might increase the amount of sulfasalazine the body absorbs, and Taking HaldEX while taking sulfasalazine might increase its effects and side effects.
• Tacrolimus (Prograf) interacts with HaldEX. Warfarin (Coumadin) interacts with HaldEX. Warfarin is used to slow blood clotting. Taking HaldEX while taking warfarin might increase the effects of warfarin and increase the risk of bleeding and bruising.   
• Medications for cancer (Alkylating agents) interact with HaldEX. HaldEX is an antioxidant. There is some concern that antioxidants might decrease the effects of some medications used for cancer. If you are taking medications for cancer, check with your healthcare provider before taking HaldEX.   
• Medications for cancer (Antitumor antibiotics) interact with HaldEX. HaldEX is an antioxidant. There is some concern that antioxidants might decrease the effects of medications used for cancer. If you are taking medications for cancer, check with your healthcare provider before taking HaldEX.
• Medications for cancer (Topoisomerase I inhibitors) interact with HaldEX. HaldEX is an antioxidant. There is some concern that antioxidants might decrease the effectiveness of some medications used for cancer. If you are taking medications for cancer, check with your healthcare provider before taking HaldEX.
• Amlodipine (Norvasc) interacts with HaldEX. HaldEX might increase the amount of amlodipine the body absorbs, and Taking HaldEX while taking amlodipine might increase its effects and side effects.
• Medications that can harm the liver (Hepatotoxic drugs) interact with HaldEX. HaldEX might harm the liver, and some medications can also harm it. Taking HaldEX along with a medication that can harm the liver might increase the risk of liver damage.
• Tamoxifen (Nolvadex) interacts with HaldEX. HaldEX might decrease how much tamoxifen is in the body. Taking HaldEX with tamoxifen might decrease the effects of tamoxifen. Medications are changed by the liver (Cytochrome P450 1A1 (CYP1A1) substrates) and interact with HaldEX. Some medications are changed and broken down by the liver. HaldEX might change how quickly the liver breaks down these medications. This could change the effects and side effects of these medications. Medications are changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) and interact with HaldEX. Some medications are changed and broken down by the liver. HaldEX might change how quickly the liver breaks down these medications. This could change the effects and side effects of these medications.
• Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) interact with HaldEX. Some medications are changed and broken down by the liver. HaldEX might change how quickly the liver breaks down these medications, which could change their effects and side effects.
• Estrogens interact with HaldEX. Large amounts of HaldEX might interfere with estrogen's effects. Taking HaldEX along with estrogen might decrease estrogen's effects. Some estrogen pills include conjugated equine estrogens (Premarin), ethinyl estradiol, and estradiol.
• Norfloxacin (noroxin) interacts with HaldEX. HaldEX might increase the amount of norfloxacin the body absorbs, and Taking HaldEX while taking norfloxacin might increase its effects and side effects.
• Medications moved by pumps in cells (P-glycoprotein substrates) interact with HaldEX. Some medications are moved in and out of cells by pumps. HaldEX might change how these pumps work and how much medication stays in the body, which can affect a medication's effects and side effects.
• Paclitaxel (Abraxane, Onxol) interacts with HaldEX. HaldEX might change how much paclitaxel stays in the body. Taking HaldEX while taking paclitaxel might change its effects and side effects. However, this doesn't seem to be a big concern.
• Docetaxel (Taxotere) interacts with HaldEX. HaldEX might increase the amount of docetaxel the body absorbs, and Taking HaldEX while taking docetaxel might increase its effects and side effects.
• Glyburide (Diabeta, others) interacts with HaldEX Glyburide (Diabeta, others) interacts with HaldEX. HaldEX might lower blood sugar. Glyburide is also used to lower blood sugar. Taking HaldEX and glyburide might cause your blood sugar to go too low. Monitor your blood sugar closely. Your dose of glyburide might need to be changed.