Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment.

Painful distal symmetric polyneuropathy (DSPN) is one of the most common complications of type 2 diabetes mellitus (T2DM), affecting quality of life and increasing the disease burden. Standard pharmacological treatments often provide suboptimal relief and may cause adverse effects, highlighting the need for alternative therapies. Electroacupuncture (EA), a traditional Chinese medicine technique, has shown promising clinical outcomes in pain reduction, but its role in diabetic neuropathy remains underexplored. This pilot clinical trial aimed to assess the efficacy of EA in reducing neuropathic pain in patients with T2DM and axonal DSPN. We conducted a pilot randomized, double-blind, sham-controlled trial in northern Mexico City (December 2021-August 2023). Eighteen patients with clinically and electrophysiologically confirmed axonal DSPN were randomly assigned to receive either true EA or sham EA, twice weekly for eight weeks (16 sessions, 20 min each). Neuropathic pain was evaluated using the Douleur Neuropathique en 4 Questions (DN-4) and Numeric Rating Scale (NRS) at baseline and post-intervention. After 16 sessions, the median DN-4 score change was not significant in either group. In contrast, the NRS scores showed reductions in the EA group: -2.78 points for current pain intensity (-58% from baseline, p = 0.028), -2.11 for least pain (-40%, p = 0.028), -4 for worst pain (-19%, p = 0.050), and -3.67 for average pain (-63%, p < 0.001). No significant changes were observed in the sham EA group. No adverse effects were reported. This pilot randomized clinical trial suggests that EA may reduce pain intensity compared to sham EA in patients with painful DSPN. However, these findings should be regarded as hypothesis-generating given the limited sample size. Larger, multicentre trials are needed to confirm these results and explore underlying mechanisms. CNIC-IMSS (R-2020-785-070; registered prospectively on May 26th, 2020), CONBIOÉTICA (09CEI00920160601), COFEPRIS (CI: 17 CI 09 015 006), ClinicalTrials.gov (NCT05521737; retrospectively registered on August 30th, 2022; first participant enrolled December 2021), and the International Clinical Trials Registry platform (ISRCTN97391213, retrospectively registered on September 12th, 2022).

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML.

Background: Acute myeloid leukemia (AML) is a hematological neoplasm of rapid and progressive onset, and is the most common form of leukemia in adults. Chemoresistance to conventional treatments such as cytarabine (Ara-C) and daunorubicin is a main cause of relapse, recurrence, metastasis, and high mortality in AML patients. It is known that sodium caseinate (SC), a salt derived from casein, a milk protein, inhibits growth and induces apoptosis in acute myeloid leukemia cells but not in normal hematopoietic cells. However, it is unknown whether SC retains its antileukemic effect in cytarabine-resistant AML cell lines. Objective: To evaluate the antineoplastic effect of SC in cytarabine-resistant leukemia models. Methods: The SC inhibits the growth and induces apoptosis in parental WEHI-3 AML cells. Here, we generated two cytarabine-resistant sublines, WEHI-CR25 and WEHI-CR50, which exhibit 6- and 16-fold increased resistance to cytarabine, respectively, compared to the parental WEHI-3 cells. Thus, these sublines mimic a chemoresistant model. Results: We demonstrate that WEHI-CR25 and WEHI-CR50 cells retain sensitivity to SC, similar to parental WEHI-3 cells. This sensitivity results in inhibited cell proliferation, induced apoptosis, and increased expression of ENT1 and dCK, molecules involved in the entry and metabolism of Ara-C, while decreasing MDR1 expression. Additionally, we observed that SC prolonged the survival of WEHI-CR50 tumor-bearing mice, despite their resistance to Ara-C. Conclusion: This is the first evidence that SC, a milk protein, may inhibit proliferation and induce apoptosis in cytarabine-resistant cells.

Chemoresistance is the leading cause of mortality in cancer patients. The poor clinical prognosis and limited therapeutic options for acute myeloid leukemia (AML) patients demand the development of new therapeutic strategies capable of overcoming chemoresistance and avoiding toxic side effects in normal cells. Sodium caseinate (SC), a derivative of casein protein found in milk, has demonstrated a dual role: it inhibits the proliferation of several murine AML cell lines while promoting the proliferation of normal hematopoietic cells. Furthermore, we previously showed that SC can modulate the expression of genes associated with chemoresistance in mouse cells. However, its biological effects on cytarabine-resistant human leukemia cells remain unclear. Here, we developed the HL60-CR50 subline, resistant to cytarabine, and investigated the effects of SC. We demonstrated that SC significantly reduced cell proliferation, decreased SIRT1 levels, increased acetylated p53, activated cleaved caspase-3, and enhanced apoptosis in cytarabine-resistant cells. These findings suggest that SC might have potential as a therapeutic adjuvant for AML, providing efficacy in chemoresistant cases compared with cytarabine treatment alone.

Polycystic ovary syndrome (PCOS) is one of the most common metabolic–endocrine disorders affecting women of reproductive age and represents a significant public health concern due to its clinical heterogeneity. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently associated with hyperinsulinemia, obesity, dyslipidemia, chronic low-grade inflammation, and an increased risk of type 2 diabetes and cardiovascular disease. Conventional treatments, including combined oral contraceptives, metformin, and ovulation-inducing agents, primarily target symptoms and present limitations in efficacy, tolerability, and their ability to address underlying metabolic dysfunction. In this context, naturally derived bioactive compounds have emerged as promising complementary therapeutic strategies. Various phytochemicals exhibit antioxidant, anti-inflammatory, hypoglycemic, and reproductive axis-modulating effects by targeting key molecular pathways involved in insulin resistance, hyperandrogenism, and follicular dysfunction. Emerging preclinical and clinical evidence suggests that these compounds may improve metabolic, hormonal, and reproductive outcomes in women with PCOS.